Gastric juice ZC3H13 as a potential biomarker for gastric cancer

Gastric juice ZC3H13 as a potential biomarker for gastric cancer | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Gastric juice ZC3H13 as a potential biomarker for gastric cancer Zhengjie Zhang, Qianyu Liu, Yuan Zhu, Qingqing Yang, Kangchen Zhang, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7364885/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective To investigate the expression of the m6A methyltransferase ZC3H13 in the gastric juice of patients with various gastric diseases and its potential diagnostic value for gastric cancer. Method Detection of gastric juice ZC3H13 expression levels of 126 patients with gastric cancer, gastric ulcer, chronic atrophic gastritis, and chronic non-atrophic gastritis using ELISA. The diagnostic potential of gastric juice ZC3H13 as a biomarker for gastric cancer was evaluated by constructing receiver operating characteristic (ROC) curves. Additionally, the diagnostic efficacy of combining gastric juice ZC3H13 detection with the traditional serum biomarker carcinoembryonic antigen (CEA) for gastric cancer was further explored. Concurrently, the expression levels of gastric juice ZC3H13 were examined to assess its diagnostic capability for early-stage gastric cancer. Finally, the correlation between gastric juice ZC3H13 and the clinical pathological characteristics of gastric cancer patients was analyzed using a chi-square( χ 2 ) test. Results The expression levels of gastric juice ZC3H13 in the patients with gastric cancer was significantly lower than that of patients with gastric ulcers, chronic atrophic gastritis, and chronic non-atrophic gastritis. Analysis of gastric cancer patients revealed that the expression level of gastric juice ZC3H13 was significantly correlated with tumor infiltration degree, lymph node metastasis, distant metastasis, and TNM staging ( P < 0.05). The area under the ROC curve (AUC) of gastric juice ZC3H13 for diagnosing gastric cancer was 0.933, with a sensitivity of 88.9% and a specificity of 90.5%. The expression level of gastric juice ZC3H13 in the patients with early gastric cancer was higher than that of those with locally advanced and advanced gastric cancer. The AUC value for distinguishing early gastric cancer was 0.784, with a sensitivity of 76.2% and a specificity of 76.2%. The AUC value for the combined detection of gastric juice ZC3H13 and CEA for detecting gastric cancer was 0.958, with a sensitivity of 89.2% and a specificity of 96.8%. Conclusion Gastric juice ZC3H13 is under-expressed in gastric cancer patients, and its expression level is higher in early gastric cancer patients compared to locally advanced and advanced gastric cancer patients. This suggests that gastric juice ZC3H13 may have clinical application value in the diagnosis of gastric cancer, including early gastric cancer. gastric cancer Liquid biopsy Gastric juice ZC3H13 M6A methyltransferase Figures Figure 1 Figure 2 Figure 3 Figure 4 1 Introduction Gastric cancer is one of the most common tumors, with a high incidence and mortality rate worldwide[ 1 ]. Due to the absence of typical symptoms and specific diagnostic markers in early-stage gastric cancer, its early diagnosis rate remains relatively low[ 2 ]. Currently, endoscopic tissue biopsy is regarded as the gold standard for diagnosing gastric cancer[ 3 ]; however, this method has limitations, including a certain rate of missed diagnoses, significant invasiveness, an inability to fully reflect tumor heterogeneity, and poor reproducibility. In contrast, liquid biopsy is not only easy to perform, minimally invasive, and highly reproducible but also integrates tumor information from multiple spaces and stages, maximizing the capture of tumor heterogeneity and effectively compensating for the shortcomings of endoscopic examination. Therefore, it has become a promising detection method[ 4 – 6 ]. Liquid biopsy, traditionally based on blood samples, has significantly advanced the early diagnosis, ongoing detection, precise treatment, screening for drug resistance, and prognosis evaluation of gastric cancer. Nonetheless, it still suffers from drawbacks such as low specificity and limited clinical application value[ 7 , 8 ]. Gastric juice, secreted directly by the gastric mucosa, is rich in numerous shed tumor cells and tumor metabolism-related substances, and its contents are subject to dynamic changes. Real-time monitoring of biomarker changes in gastric juice can offer critical insights into disease progression, treatment response, and the overall management of gastric cancer patients, thereby facilitating personalized treatment[ 9 ]. Traditional biomarkers have shown low sensitivity and specificity in diagnosing gastric cancer, particularly in its early stages[ 10 , 11 ]. Consequently, employing gastric fluid biopsy technology to identify biomarkers that are highly sensitive and specific is crucial for reducing the rate of missed diagnoses in early gastric cancer and enabling early and effective diagnosis. N6-methyladenosine (m6A) mRNA modification is the most prevalent epigenetic modification in eukaryotes. Zinc finger CCCH domain-containing protein 13 (ZC3H13) is a recently identified m6A methyltransferase[ 12 , 13 ]. Studies have indicated that ZC3H13 is implicated in the onset and progression of gastric cancer; however, its precise mechanism and role in gastric cancer remain unclear[ 14 ]. Our team's preliminary research revealed that the expression level of ZC3H13 in gastric cancer tissues is significantly elevated compared to that in adjacent normal tissues, and the concentration of ZC3H13 in the blood of patients with gastric cancer is markedly higher than in healthy individuals[ 15 ]. This suggests that ZC3H13 may play a pivotal role in the onset and progression of gastric cancer and holds certain clinical diagnostic potential. It is anticipated to emerge as one of the novel diagnostic biomarkers for gastric cancer, albeit with relatively low specificity. The objective of this study is to investigate the potential of ZC3H13 in gastric juice as an early diagnostic biomarker for gastric cancer by assessing its expression levels in patients with various gastric diseases. 2 Data and Methods 2.1 Case Data Between March 2023 and March 2024, 63 patients who underwent electronic gastroscopy at the 940 Hospital of the Joint Service Support Force of the Chinese People's Liberation Army and Liangzhou Hospital of Wuwei City and were definitively diagnosed with gastric cancer through pathology were selected as the experimental group. The control group consisted of 29 patients with gastric ulcers, 12 with chronic atrophic gastritis, and 22 with chronic non-atrophic gastritis who also underwent electronic gastroscopy during the same period. Gastric juice samples and clinical data from these patients were collected. Tumor clinical stages were assessed according to Tumor-Node-Metastasis (TNM) staging system (8th ed.). 2.2 Reagents The ZC3H13 ELISA kit was purchased from Jiangsu Enzyme Labeling Biotechnology Co.Ltd. in China. 2.3 Specimen Preparation Gastric juice samples (10 ml each) from patients with gastric cancer, gastric ulcer, chronic atrophic gastritis, and chronic non-atrophic gastritis were collected through electronic gastroscopy examination, centrifuged at 3000 r/min for 10 minutes, and the supernatant was taken and stored in a -80°C freezer for future use. 2.4 Detection of ZC3H13 Protein in Gastric Juice An enzyme-linked immunosorbent assay (ELISA) was used for detection with the ZC3H13 kit, with a correlation coefficient R ≥ 0.99; the detection range is 1.0 ~ 160 ng/mL; the minimum detectable concentration is less than 1.0 ng/mL. Strict adherence to the reagent kit instructions is necessary for operation. The absorbance (OD value) of each well was measured sequentially at a wavelength of 450 nm using an ELISA reader. 2.5 Statistical Methods Conduct statistical analysis and create plots using SPSS 25.0 and GraphPad Prism 8. The expression level of ZC3H13 in normally distributed quantitative data is presented as mean ± standard deviation (x ± s), and one-way analysis of variance is employed for intergroup comparisons. Count data, including gender, tumor location, and differentiation degree, are presented as n (%), and group comparisons are conducted using a chi-square ( χ 2 ) test. Receiver operating characteristic (ROC) curves are utilized to evaluate the diagnostic value of gastric juice ZC3H13 for gastric cancer and early gastric cancer, as well as the diagnostic value of combined detection of gastric juice ZC3H13 and carcinoembryonic antigen (CEA) for gastric cancer. 3 Results 3.1 Analysis of Gastric Juice ZC3H13 Expression Levels in Gastric Cancer Patients and Benign Stomach Disease Patients The ELISA method was employed to assess the expression level of gastric juice ZC3H13 in patients with gastric cancer and those with benign stomach diseases. The findings indicated that the expression level of gastric juice ZC3H13 in patients with gastric cancer (1.80 ± 0.28) was notably lower than that of patients with gastric ulcers (2.54 ± 0.23), chronic atrophic gastritis (2.36 ± 0.25), and chronic non-atrophic gastritis (2.30 ± 0.23). The difference was statistically significant (F = 65.452, P < 0.001). However, there was no significant difference in the concentration of gastric juice ZC3H13 among patients with gastric ulcers, chronic atrophic gastritis, and chronic non-atrophic gastritis, as depicted in Fig. 1 . 3.2 Diagnostic Efficacy of Gastric Juice ZC3H13 for Gastric Cancer To further evaluate the efficacy of gastric juice ZC3H13 in diagnosing gastric cancer, an ROC curve was constructed for analysis. The results indicated that at a concentration of 2.12 ng/mL of gastric juice ZC3H13, the area under the curve (AUC) for differentiating between patients with gastric cancer and those without was 0.933 [95% confidence interval (CI): 0.888–0.977], with a sensitivity of 88.9% and a specificity of 90.5%. For more details, refer to Fig. 2 . 3.3 Diagnostic Value of Combined Gastric Juice ZC3H13 and CEA Further research had revealed that the combination of gastric juice ZC3H13 and the traditional serum tumor marker CEA enhances the diagnostic efficacy for gastric cancer. The AUC value of the constructed ROC curve was 0.958 (95% CI, 0.925–0.991), with a sensitivity of 89.2% and a specificity of 96.8%. For further details, refer to Fig. 3 . 3.4 Diagnostic Efficacy of Gastric Juice ZC3H13 for Early Gastric Cancer To investigate the potential of gastric juice ZC3H13 in diagnosing early gastric cancer, patients were categorized into two groups: early gastric cancer (TNM stage I), locally advanced gastric cancer and advanced gastric cancer (TNM stages II-IV). The findings indicated that the expression level of gastric juice ZC3H13 was significantly elevated in early gastric cancer compared to locally advanced and advanced gastric cancer (t = 3.051, P = 0.003), as shown in Fig. 4 a. The AUC was 0.784 (95% CI 0.670–0.898), the sensitivity and specificity were both 76.2% (refer to Fig. 4 b). 3.5 Correlation Analysis Between the Expression of Gastric Juice ZC3H13 and the Clinical Pathological Characteristics of Gastric Cancer Patients A study investigating the correlation between gastric juice ZC3H13 and the clinical pathological characteristics of gastric cancer patients revealed that gastric juice ZC3H13 levels were associated with tumor infiltration depth, lymph node metastasis, distant metastasis, TNM staging, and CEA levels (( P 0.05). Tab.1 Correlation analysis between gastric juice ZC3H13 expression level and clinical pathological characteristics of gastric cancer patients Clinicopathological features n (%) ZC3H13 χ 2 /F P Sex Male Female 23 (36.5) 40 (63.5) 1.85±0.32 1.77±0.25 0.949 0.342 Age (year) ＜60 ≥60 21 (33.3) 42 (66.7) 1.77±0.27 1.82±0.28 0.627 0.531 Smoking No Yes 40 (63.5) 23 (36.5) 1.82±0.30 1.76±0.24 0.928 0.353 Drinking No Yes 48 (76.2) 15 (23.8) 1.82±0.28 1.73±0.26 1.194 0.232 Tumor location Gastric cardia and fundus Gastric body Gastric antrum 11 (17.7) 26 (41.9) 25 (40.3) 1.76±0.26 1.79±0.23 1.82±0.34 0.125 0.940 Differentiation High Moderate Low 15 (23.8) 19 (30.2) 29 (46.0) 1.93±0.33 1.80±0.30 1.73±0.21 3.661 0.160 Invasion depth T1 T2 21 (33.3) 16 (25.4) 1.94±0.25 1.82±0.32 12.357 0.006 T3 10 (15.9) 1.66±0.20 T4 16 (25.4) 1.68±0.22 Lymph node metastasis No Yes 28 (44.4) 35 (55.6) 1.92±0.28 1.70±0.24 3.205 0.001 Distant metastases No Yes 51 (81.0) 12 (19.0) 1.85±0.28 1.60±0.17 2.748 0.006 TNM stage Ⅰ Ⅱ 24 (38.1) 11 (17.5) 1.96±0.27 1.79±0.28 16.565 0.001 Ⅲ 16 (25.4) 1.71±0.22 Ⅳ 12 (19.0) 1.60±0.17 CEA (μg/L) ＜5 ≥5 51 (81.0) 12 (19.0) 1.84±0.28 1.62±0.19 2.599 0.009 CA 199 (μg/L) ＜37 ≥37 51 (81.0) 12 (19.0) 1.82±0.26 1.76±0.34 0.919 0.358 4 Discussion In recent years, m6A methylation modification has been confirmed as a key regulatory mechanism in gastric cancer[ 16 ]. ZC3H13, a type of m6A methyltransferase, plays a crucial role in the occurrence and development of tumors[ 17 ]. Some studies have found that ZC3H13 may participate in the occurrence and development of various tumors as either a pro-cancer or anti-cancer factor. For instance, a study by Zhu et al[ 18 ] found that ZC3H13 is downregulated in colorectal cancer tissues, suggesting that it can act as an anti-cancer factor to inhibit the proliferation and invasion of rectal cancer. Its mechanism may be related to the inactivation of the Ras-ERK signaling pathway. Xie et al[ 19 ] observed that ZC3H13 is expressed at low levels in papillary thyroid carcinoma cell lines. Further investigation revealed that ZC3H13 inhibits the growth of papillary thyroid carcinoma by mediating the m6A modification-induced degradation of GTPase activating protein 1 (IQGAP1) containing IQ motifs. Wang et al[ 20 ] monitored the expression of ZC3H13 in liver cancer and adjacent normal tissues, noting that ZC3H13 was downregulated in liver cancer tissues. Through m6A-PKM2-mediated glycolysis, ZC3H13 inhibited the progression of liver cancer and increased the sensitivity of liver cancer cells to cisplatin. In the context of gastric cancer, researchers have found that ZC3H13 is involved in the occurrence and development of the disease[ 12 ]. For example, McGrail et al[ 21 ] observed that the expression level of ZC3H13 in gastric cancer tissue was significantly increased. ZC3H13 silencing can inhibit the proliferation, migration, and invasion ability of gastric cancer cells, although the specific molecular mechanism remains unclear. Our research group has previously discovered that the ZC3H13 protein is highly expressed in blood and tissues, and it has the potential to serve as a diagnostic biomarker for gastric cancer. However, its specificity is relatively low[ 15 ] at 50%. Gastric juice is secreted directly by the gastric mucosa and contains numerous shed tumor cells and tumor metabolism-related substances. Moreover, the contents of gastric juice are dynamically changing, with the composition and biomarkers varying with the disease state. By collecting and analyzing gastric juice, lesions or abnormalities that might be missed during endoscopic examination can be detected[ 7 , 22 , 23 ]. Furthermore, real-time monitoring of biomarker changes in gastric juice can provide valuable insights into disease progression, treatment response, and overall management of gastric cancer patients, facilitating personalized treatment goals[ 24 , 25 ]. Currently, researchers have isolated extracellular vesicles, long non-coding RNAs, DNA, and proteins from gastric juice. They have found that liquid biopsy techniques using gastric juice as the detection sample exhibit higher sensitivity and specificity compared to those using blood, and they better represent the heterogeneity of gastric cancer[ 26 ]. Zhou et al[ 27 ] studied 66 gastric cancer patients and 66 healthy individuals, using qRT-PCR to measure the expression of piR-1245 in gastric juice and tissues. The results indicated that the level of piR-1245 in the gastric juice of gastric cancer patients was significantly higher than in healthy individuals ( p < 0.01), and the expression of piR-1245 in gastric juice and tissues was consistent. Gastric juice piR-1245 can differentiate gastric cancer patients from healthy individuals, with an AUC value of 0.885, surpassing CEA (AUC value of 0.642) and CA724 (AUC value of 0.673). Another study found that H19[ 28 ] and miR-92a−3p[ 29 ] in gastric juice are not only closely related to the diagnosis of gastric cancer but also that their expression levels correlate with the classification and staging of gastric cancer, making them potential prognostic markers for the disease. This study initially detected the expression of gastric juice ZC3H13 in the patients with gastric cancer, gastric ulcer, chronic atrophic gastritis, and chronic non-atrophic gastritis. We found that the expression level of gastric juice ZC3H13 in the gastric cancer patients was lower than that of patients with gastric ulcers, chronic atrophic gastritis, and chronic non-atrophic gastritis. However, there was no significant difference in the expression level of gastric juice ZC3H13 in the patients with gastric ulcers, chronic atrophic gastritis, and chronic non-atrophic gastritis. The ROC curve results for gastric juice ZC3H13 in diagnosing gastric cancer showed that the sensitivity and specificity of gastric juice ZC3H13 in distinguishing gastric cancer patients from non-gastric cancer patients were 88.9% and 90.5%, respectively, indicating high clinical value. Meanwhile, the sensitivity and specificity of the combination of gastric juice ZC3H13 and the traditional tumor marker CEA in diagnosing gastric cancer were 89.2% and 96.8%, respectively, suggesting that gastric juice ZC3H13 is closely related to gastric cancer and has the potential to serve as a diagnostic marker for the disease. Our research group previously discovered that the ZC3H13 protein is highly expressed in blood and tissues. However, this study indicates that the expression level of ZC3H13 is reduced in the gastric juice of gastric cancer patients, which contradicts earlier findings. The discrepancy between the protein expression levels in gastric juice and those in tissues and blood warrants our attention and necessitates further investigation to understand the underlying causes. Similar observations have been made in other studies. In 2013, Cui et al[ 30 ] utilized real-time quantitative reverse transcription polymerase chain reaction to determine that the expression levels of circulating miR-21 and miR-106a in the gastric juice of gastric cancer patients were significantly lower than those in patients with benign gastric diseases. Conversely, gastric mucosal biopsy results indicated that the expression levels of circulating miR-21 and miR-106a were elevated in the plasma and tissues of gastric cancer patients. Shao et al[ 31 ] conducted another study where they examined the expression levels of hsa_circ_0065149 in the gastric juice of gastric cancer patients, chronic atrophic gastritis patients, gastric ulcer patients, and healthy volunteers. They also observed inconsistencies between the expression levels in gastric juice and those in plasma and tissue. They suggest that this contrasting trend may be associated with the function of exosomes. The poor prognosis of gastric cancer is largely attributed to the absence of highly sensitive and specific early diagnostic strategies. Endoscopy remains the primary method for diagnosing early gastric cancer, but its invasiveness and high cost restrict its use for screening purposes. Traditional blood markers such as CEA, CA199, and pepsinogen have extremely low diagnostic value for early gastric cancer[ 32 ]. Liquid biopsy is a novel technique that has the potential to improve the early diagnosis rate of gastric cancer. However, due to the limited number of components in the body fluids of patients with early gastric cancer, the detection rate is low, and the application of liquid biopsy for gastric cancer screening and early diagnosis still faces challenges. Hee et al[ 33 ] analyzed the levels of microbial-derived extracellular vesicles (EVs) in the gastric juice and other body fluids of patients with low-grade dysplasia, high-grade dysplasia, and gastric cancer. The study found that as the disease progressed, the microbial diversity in gastric juice and serum samples significantly changed. In gastric juice, the abundance of C. acnes and S. oralis showed a significant increase with the progression of disease severity. These findings underscore the potential of microbial-derived EVs as early diagnostic tools for gastric cancer and its precursors. Wang et al[ 5 ] used ELISA to detect the levels of aldehyde dehydrogenase 1 and gastrin 17 in the gastric juice of patients with various gastric diseases. The research results indicated that the levels of aldehyde dehydrogenase 1 and gastrin 17 in the gastric juice of gastric cancer patients were higher than those of patients with gastric ulcers and gastritis. Additionally, the levels of these markers in gastric ulcer patients were higher than those in gastritis patients. The AUC values for aldehyde dehydrogenase 1, gastrin 17, and the combination of both markers in gastric juice for the diagnosis of gastric cancer were 0.695, 0.759, and 0.792, respectively. Our study found that the area under the ROC curve for gastric juice ZC3H13 in distinguishing early gastric cancer from advanced gastric cancer was 0.784, with a sensitivity of 76.2% and a specificity of 76.2%. This result suggests that gastric juice ZC3H13 has certain reference value for the diagnosis of early gastric cancer and may offer a new strategy for the early screening of gastric cancer. This study also found that the expression level of gastric juice ZC3H13 is closely related to the clinical and pathological characteristics of gastric cancer patients, such as tumor infiltration depth, lymph node metastasis, distant metastasis, and TNM staging, further confirming the important role of gastric juice ZC3H13 in the progression of gastric cancer. Although this study has achieved certain results, there are still some limitations. For instance, the relatively small sample size included in this study may affect the stability and reliability of the results. In the future, we plan to expand the sample size and conduct multicenter, prospective studies to validate the clinical value of gastric juice ZC3H13 as a diagnostic biomarker for gastric cancer. Simultaneously, we will also explore the specific molecular mechanisms and trends of gastric juice ZC3H13 in the occurrence and development of gastric cancer, providing new targets and treatment strategies for the treatment of gastric cancer. 5 Conclusion Gastric juice ZC3H13, as a potential diagnostic biomarker for gastric cancer, has high sensitivity and specificity and is expected to become an important tool for early screening and diagnosis of gastric cancer. In the future, we will continue to conduct in-depth research on the diagnostic value and therapeutic potential of gastric juice ZC3H13 in gastric cancer, contributing more to the prevention and treatment of gastric cancer. Declarations Consent to publish All authors read and approved to publish the final manuscript. Competing interests The authors declare no competing interests. Funding Wuwei Science and Technology Bureau (project number WW24B01SF087). Data availability Data supporting the findings of this study are available from the corresponding author upon reasonable request. Ethics approval and Consent to participate This study was approved by the Ethics Committee of 940th Hospital of Joint Logistics Support Force of People's Liberation Army (No. 2023KYLL345) and was performed in accordance with the ethical standards described in the Declaration of Helsinki. Informed consent for this study was obtained using the opt-out system with the approval of the ethics committee. Consent to participate Informed consent was obtained from the participants to participate in the current study. Author Contribution XZ Wei and YH Liu designed the study. ZJ Zhang performed the work and drafted the manuscript, QY Liu, Y Zhu, QQ Yang, KC Zhang, AF Duo and SS Ding collection and interpretation of specimen data and refined the drafted manuscript. References Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2024,74(3):229-263. Smyth E C, Nilsson M, Grabsch H I, et al. Gastric cancer[J]. Lancet, 2020,396(10251):635-648. Hiramatsu T, Kakushima N, Kuribara H, et al. Recent advancement in endoscopic diagnosis for risk stratification of gastric cancer[J]. Clin Endosc, 2025. Lone S N, Nisar S, Masoodi T, et al. Liquid biopsy: a step closer to transform diagnosis, prognosis and future of cancer treatments[J]. Mol Cancer, 2022,21(1):79. Wang Y, Liu H, Li X, et al. Study on the value of gastrin 17 and aldehyde dehydrogenase 1 in gastric juice for early diagnosis in gastric cancer[J]. Front Oncol, 2025,15:1521868. Gasparello J, Ceccon C, Angerilli V, et al. Liquid biopsy in gastric cancer: A snapshot of the current state of the art[J]. J Liq Biopsy, 2025,7:100288. Roy S, Kanda M, Nomura S, et al. Diagnostic efficacy of circular RNAs as noninvasive, liquid biopsy biomarkers for early detection of gastric cancer[J]. Mol Cancer, 2022,21(1):42. Wang H, Zhang Y, Zhang H, et al. Liquid biopsy for human cancer: cancer screening, monitoring, and treatment[J]. MedComm (2020), 2024,5(6):e564. Skryabin G, Enikeev A, Beliaeva A, et al. Distinctive Features of Extracellular Vesicles Present in the Gastric Juice of Patients with Gastric Cancer and Healthy Subjects[J]. Int J Mol Sci, 2025,26(12). Wu D, Zhang P, Ma J, et al. Serum biomarker panels for the diagnosis of gastric cancer[J]. Cancer Med, 2019,8(4):1576-1583. Herrera-Pariente C, Montori S, Llach J, et al. Biomarkers for Gastric Cancer Screening and Early Diagnosis[J]. Biomedicines, 2021,9(10). Meijing Z, Tianhang L, Biao Y. N6-Methyladenosine Modification Patterns and Tumor Microenvironment Immune Characteristics Associated With Clinical Prognosis Analysis in Stomach Adenocarcinoma[J]. Front Cell Dev Biol, 2022,10:913307. Huang J, Shao Y, Gu W. Function and clinical significance of N6-methyladenosine in digestive system tumours[J]. Exp Hematol Oncol, 2021,10(1):40. Han Y, Sun J, Yao M, et al. Biological roles of enhancer RNA m6A modification and its implications in cancer[J]. Cell Commun Signal, 2025,23(1):254. Jia LJ, Zhang YQ, Zhang BH, etc Expression and clinical significance of m~6A methyltransferase ZC3H13 in gastric cancer tissue and serum [J]. Cancer Prevention and Treatment Research, 2022, 49 (08): 792-798. Ding S Q, Zhang X P, Pei J P, et al. Role of N6-methyladenosine RNA modification in gastric cancer[J]. Cell Death Discov, 2023,9(1):241. Gao L, Gao J, He J, et al. Identification of m6A methyltransferase-related WTAP and ZC3H13 predicts immune infiltrates in glioblastoma[J]. Sci Rep, 2025,15(1):4412. Zhu D, Zhou J, Zhao J, et al. ZC3H13 suppresses colorectal cancer proliferation and invasion via inactivating Ras-ERK signaling[J]. J Cell Physiol, 2019,234(6):8899-8907. Xie R, Chen W, Lv Y, et al. Overexpressed ZC3H13 suppresses papillary thyroid carcinoma growth through m6A modification-mediated IQGAP1 degradation[J]. J Formos Med Assoc, 2023. Wang Q, Xie H, Peng H, et al. ZC3H13 Inhibits the Progression of Hepatocellular Carcinoma through m(6)A-PKM2-Mediated Glycolysis and Enhances Chemosensitivity[J]. J Oncol, 2021,2021:1328444. McGrail D J, Pilié P G, Rashid N U, et al. High tumor mutation burden fails to predict immune checkpoint blockade response across all cancer types[J]. Ann Oncol, 2021,32(5):661-672. Lianos G D, Kyrochristou G D, Lianou A D, et al. Gastric Juice Biomarkers in Gastric Cancer: New Trends?[J]. Maedica (Bucur), 2024,19(4):775-779. You H S, Park J Y, Seo H, et al. Increasing correlation between oral and gastric microbiota during gastric carcinogenesis[J]. Korean J Intern Med, 2024,39(4):590-602. Onoyama T, Ishikawa S, Isomoto H. Gastric cancer and genomics: review of literature[J]. J Gastroenterol, 2022,57(8):505-516. Si Y T, Xiong X S, Wang J T, et al. Identification of chronic non-atrophic gastritis and intestinal metaplasia stages in the Correa's cascade through machine learning analyses of SERS spectral signature of non-invasively-collected human gastric fluid samples[J]. Biosens Bioelectron, 2024,262:116530. Felípez N, Montori S, Mendizuri N, et al. The Human Gastric Juice: A Promising Source for Gastric Cancer Biomarkers[J]. Int J Mol Sci, 2023,24(11). Zhou X, Liu J, Meng A, et al. Gastric juice piR-1245: A promising prognostic biomarker for gastric cancer[J]. J Clin Lab Anal, 2020,34(4):e23131. Chen J S, Wang Y F, Zhang X Q, et al. H19 serves as a diagnostic biomarker and up-regulation of H19 expression contributes to poor prognosis in patients with gastric cancer[J]. Neoplasma, 2016,63(2):223-230. Liu L, Dai A, Zhang Z, et al. LncRNA PITPNA-AS1 promotes gastric cancer by increasing SOX4 expression via inhibition of miR-92a-3p[J]. Aging (Albany NY), 2021,13(17):21191-21201. Cui L, Zhang X, Ye G, et al. Gastric juice MicroRNAs as potential biomarkers for the screening of gastric cancer[J]. Cancer, 2013,119(9):1618-1626. Shao Y, Tao X, Lu R, et al. Hsa_circ_0065149 is an Indicator for Early Gastric Cancer Screening and Prognosis Prediction[J]. Pathol Oncol Res, 2020,26(3):1475-1482. Conti C B, Agnesi S, Scaravaglio M, et al. Early Gastric Cancer: Update on Prevention, Diagnosis and Treatment[J]. Int J Environ Res Public Health, 2023,20(3). You H S, Park J Y, Seo H, et al. Distinct microbial signatures of liquid biopsy samples during gastric carcinogenesis and insights from extracellular vesicle analysis[J]. Korean J Intern Med, 2025,40(4):571-583. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7364885","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":515927875,"identity":"43052cb8-00f0-4ea7-a1a7-023e844dbb49","order_by":0,"name":"Zhengjie Zhang","email":"","orcid":"","institution":"Wu Wei Liang Zhou Hospital","correspondingAuthor":false,"prefix":"","firstName":"Zhengjie","middleName":"","lastName":"Zhang","suffix":""},{"id":515927876,"identity":"f35dfa6e-215b-42e9-8f0d-3a5101308b7f","order_by":1,"name":"Qianyu Liu","email":"","orcid":"","institution":"Wu Wei Liang Zhou Hospital","correspondingAuthor":false,"prefix":"","firstName":"Qianyu","middleName":"","lastName":"Liu","suffix":""},{"id":515927877,"identity":"921fe679-537d-4c70-84b4-1614076ef2da","order_by":2,"name":"Yuan Zhu","email":"","orcid":"","institution":"Wu Wei Liang Zhou Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yuan","middleName":"","lastName":"Zhu","suffix":""},{"id":515927878,"identity":"e5fc479d-8ab4-43b9-ac97-388be20ab466","order_by":3,"name":"Qingqing Yang","email":"","orcid":"","institution":"Wu Wei Liang Zhou Hospital","correspondingAuthor":false,"prefix":"","firstName":"Qingqing","middleName":"","lastName":"Yang","suffix":""},{"id":515927879,"identity":"fc456c25-a5a3-4f70-addf-6b116c4eccaf","order_by":4,"name":"Kangchen Zhang","email":"","orcid":"","institution":"Wu Wei Liang Zhou Hospital","correspondingAuthor":false,"prefix":"","firstName":"Kangchen","middleName":"","lastName":"Zhang","suffix":""},{"id":515927880,"identity":"ab2670f8-1915-4c93-ba44-ff1302475d54","order_by":5,"name":"Aifeng Duo","email":"","orcid":"","institution":"Wu Wei Liang Zhou Hospital","correspondingAuthor":false,"prefix":"","firstName":"Aifeng","middleName":"","lastName":"Duo","suffix":""},{"id":515927881,"identity":"76312e8b-97c9-4e02-84a0-09e745488442","order_by":6,"name":"Shanshan Ding","email":"","orcid":"","institution":"Wu Wei Liang Zhou Hospital","correspondingAuthor":false,"prefix":"","firstName":"Shanshan","middleName":"","lastName":"Ding","suffix":""},{"id":515927882,"identity":"395c6dfd-f8da-4121-b94c-0275168878d3","order_by":7,"name":"Yinghai Liu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAvElEQVRIiWNgGAWjYBACfvnDBx98qLCp7ydai+QMtmTDGWfSGGc2EKvF4AaPmTBny2HGDQeItmV2WxozYwMzs/Hx5A0MPyq2EdbCL3P42OPCHWxsZmeeFTD2nLlNhC0NaenGM8/w8JjdyDFgZmwjQovBgRwzad42CQnjGURruQHWYmBgIEGsFsmeY6BATkiQAPrlIFF+4WdvBkXl/wT+9uSND35UEKEFCSQYHCBJPVgLqTpGwSgYBaNghAAAEutBsOfXMHoAAAAASUVORK5CYII=","orcid":"","institution":"Wu Wei Liang Zhou Hospital","correspondingAuthor":true,"prefix":"","firstName":"Yinghai","middleName":"","lastName":"Liu","suffix":""},{"id":515927883,"identity":"f3b046fe-4466-409f-8a8d-5de7092758f4","order_by":8,"name":"Xiuzhen Wei","email":"","orcid":"","institution":"Wu Wei Liang Zhou Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xiuzhen","middleName":"","lastName":"Wei","suffix":""}],"badges":[],"createdAt":"2025-08-13 12:23:15","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7364885/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7364885/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":91835393,"identity":"458bfee4-241a-4ec1-a91f-c1f1e1b847c7","added_by":"auto","created_at":"2025-09-22 09:31:08","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":224179,"visible":true,"origin":"","legend":"","description":"","filename":"GastricjuiceZC3H13asapotentialbiomarkerforgastriccancer.docx","url":"https://assets-eu.researchsquare.com/files/rs-7364885/v1/945e0d40598aa3f412a132c3.docx"},{"id":91835392,"identity":"181ade3f-b163-463a-b122-5e4769a04ddf","added_by":"auto","created_at":"2025-09-22 09:31:08","extension":"json","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":10323,"visible":true,"origin":"","legend":"","description":"","filename":"53261889e0a248e897c492448a144eb3.json","url":"https://assets-eu.researchsquare.com/files/rs-7364885/v1/590dd3683828748f40ab8761.json"},{"id":91835395,"identity":"a1300574-f425-4de1-9a7a-3f5c9091051d","added_by":"auto","created_at":"2025-09-22 09:31:08","extension":"xml","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":84606,"visible":true,"origin":"","legend":"","description":"","filename":"53261889e0a248e897c492448a144eb31enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-7364885/v1/6142447ec2f0b48ba0dc327d.xml"},{"id":91835397,"identity":"0652427e-4a14-42f2-b198-7376a565ecda","added_by":"auto","created_at":"2025-09-22 09:31:08","extension":"png","order_by":3,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":8750,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7364885/v1/6470ea91d92a76efa83b28f9.png"},{"id":91835398,"identity":"e6a5ecf9-bba1-4371-b9da-d9d167772630","added_by":"auto","created_at":"2025-09-22 09:31:08","extension":"png","order_by":4,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":8771,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7364885/v1/d575c1d0cf26ca1f74c25204.png"},{"id":91836829,"identity":"654c0da1-2710-4e0d-9810-301c66d16e0b","added_by":"auto","created_at":"2025-09-22 09:39:08","extension":"emf","order_by":5,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1763844,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage3.emf","url":"https://assets-eu.researchsquare.com/files/rs-7364885/v1/f0c89edb351af02778b6c32a.emf"},{"id":91835399,"identity":"129b69a2-f313-4b57-98d5-8dad3899aef2","added_by":"auto","created_at":"2025-09-22 09:31:08","extension":"jpeg","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1074,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage4.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7364885/v1/eedac5d36364647886f6d428.jpeg"},{"id":91838565,"identity":"870ccfb3-796c-4b1b-b63e-40f57ae9d270","added_by":"auto","created_at":"2025-09-22 09:47:08","extension":"jpeg","order_by":7,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":23123,"visible":true,"origin":"","legend":"","description":"","filename":"groupimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-7364885/v1/5380d61efba12c376b1e0137.jpeg"},{"id":91841342,"identity":"fc9afa63-e003-4ebe-a982-556cf2c9a553","added_by":"auto","created_at":"2025-09-22 09:55:32","extension":"png","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":5322,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7364885/v1/f401e87183b532748d669004.png"},{"id":91835401,"identity":"d71d5182-84f3-4316-8cf7-8a2db34278d1","added_by":"auto","created_at":"2025-09-22 09:31:08","extension":"png","order_by":9,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":6351,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7364885/v1/0453bae48d9751ea4e3c316c.png"},{"id":91836831,"identity":"a91163f9-21e2-4d1a-b5d2-1df1885441c5","added_by":"auto","created_at":"2025-09-22 09:39:08","extension":"png","order_by":10,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":8998,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-7364885/v1/f01f77cee9b9365418993ff6.png"},{"id":91836836,"identity":"5502f769-6cfd-41da-a8c8-8cd286e02105","added_by":"auto","created_at":"2025-09-22 09:39:08","extension":"png","order_by":11,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":935,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-7364885/v1/e0acf3a60e564ae1f8c3f40a.png"},{"id":91835404,"identity":"5782bfaa-1266-450d-bb58-9a2f4b26711a","added_by":"auto","created_at":"2025-09-22 09:31:08","extension":"png","order_by":12,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":7924,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinegroupimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7364885/v1/4b436033bac40e2aa237c903.png"},{"id":91835408,"identity":"caa06d7e-2a7b-44ee-87f8-1b0bf9d3bb03","added_by":"auto","created_at":"2025-09-22 09:31:08","extension":"xml","order_by":13,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":83415,"visible":true,"origin":"","legend":"","description":"","filename":"53261889e0a248e897c492448a144eb31structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7364885/v1/8ec5e5f5d5b138ebe05c84df.xml"},{"id":91835406,"identity":"2a507717-907e-4c02-aab6-d8ca0da07e3e","added_by":"auto","created_at":"2025-09-22 09:31:08","extension":"html","order_by":14,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":92938,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7364885/v1/5b453fea32b53a781ac42340.html"},{"id":91835389,"identity":"91c2de1c-9056-498e-8e97-19008d99f191","added_by":"auto","created_at":"2025-09-22 09:31:08","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":35732,"visible":true,"origin":"","legend":"\u003cp\u003eExpression of gastric juice ZC3H13 in patients with gastric cancer, gastric ulcer, chronic atrophic gastritis, and chronic superficial gastritis\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7364885/v1/e25b5681d4ffce9b95487560.jpg"},{"id":91835390,"identity":"e24ebf7b-4e23-4040-ab63-eaac5341f5f1","added_by":"auto","created_at":"2025-09-22 09:31:08","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":27985,"visible":true,"origin":"","legend":"\u003cp\u003eROC curve of gastric juice ZC3H13 distinguishing gastric cancer patients from benign stomach disease patients\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7364885/v1/4596f9e38e7c7af2a03f71cb.jpg"},{"id":91836827,"identity":"d64b9479-5f7b-4a6c-9f7b-8655158f5463","added_by":"auto","created_at":"2025-09-22 09:39:08","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":37953,"visible":true,"origin":"","legend":"\u003cp\u003eROC curve of combined detection of gastric juice ZC3H13 and CEA for the diagnosis of gastric cancer\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7364885/v1/e35d7f4eae9fd2bcded9f22f.jpg"},{"id":91835396,"identity":"f0f9c2c1-4fa9-4d45-9737-2c7d7db1b061","added_by":"auto","created_at":"2025-09-22 09:31:08","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":46206,"visible":true,"origin":"","legend":"\u003cp\u003eExpression of gastric juice ZC3H13 in gastric cancer patients. Fig.4a The expression of gastric juice ZC3H13 in early and advanced gastric cancer;Fig.4b ROC curves of gastric juice ZC3H13 for early and advanced gastric cancer.\u003c/p\u003e","description":"","filename":"4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7364885/v1/7656824ca8d4a79d03793926.jpg"},{"id":97899802,"identity":"cb26d8d6-66df-4aa3-b14f-395ee91d361e","added_by":"auto","created_at":"2025-12-10 15:44:55","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":751218,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7364885/v1/9fb3c50f-d85a-4a64-a1e9-08deba71b523.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Gastric juice ZC3H13 as a potential biomarker for gastric cancer","fulltext":[{"header":"1 Introduction","content":"\u003cp\u003eGastric cancer is one of the most common tumors, with a high incidence and mortality rate worldwide[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Due to the absence of typical symptoms and specific diagnostic markers in early-stage gastric cancer, its early diagnosis rate remains relatively low[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Currently, endoscopic tissue biopsy is regarded as the gold standard for diagnosing gastric cancer[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]; however, this method has limitations, including a certain rate of missed diagnoses, significant invasiveness, an inability to fully reflect tumor heterogeneity, and poor reproducibility. In contrast, liquid biopsy is not only easy to perform, minimally invasive, and highly reproducible but also integrates tumor information from multiple spaces and stages, maximizing the capture of tumor heterogeneity and effectively compensating for the shortcomings of endoscopic examination. Therefore, it has become a promising detection method[\u003cspan additionalcitationids=\"CR5\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eLiquid biopsy, traditionally based on blood samples, has significantly advanced the early diagnosis, ongoing detection, precise treatment, screening for drug resistance, and prognosis evaluation of gastric cancer. Nonetheless, it still suffers from drawbacks such as low specificity and limited clinical application value[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Gastric juice, secreted directly by the gastric mucosa, is rich in numerous shed tumor cells and tumor metabolism-related substances, and its contents are subject to dynamic changes. Real-time monitoring of biomarker changes in gastric juice can offer critical insights into disease progression, treatment response, and the overall management of gastric cancer patients, thereby facilitating personalized treatment[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Traditional biomarkers have shown low sensitivity and specificity in diagnosing gastric cancer, particularly in its early stages[\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Consequently, employing gastric fluid biopsy technology to identify biomarkers that are highly sensitive and specific is crucial for reducing the rate of missed diagnoses in early gastric cancer and enabling early and effective diagnosis.\u003c/p\u003e\u003cp\u003e\u003cul\u003e\u003cli\u003e\u003cp\u003eN6-methyladenosine (m6A) mRNA modification is the most prevalent epigenetic modification in eukaryotes. Zinc finger CCCH domain-containing protein 13 (ZC3H13) is a recently identified m6A methyltransferase[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Studies have indicated that ZC3H13 is implicated in the onset and progression of gastric cancer; however, its precise mechanism and role in gastric cancer remain unclear[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Our team's preliminary research revealed that the expression level of ZC3H13 in gastric cancer tissues is significantly elevated compared to that in adjacent normal tissues, and the concentration of ZC3H13 in the blood of patients with gastric cancer is markedly higher than in healthy individuals[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. This suggests that ZC3H13 may play a pivotal role in the onset and progression of gastric cancer and holds certain clinical diagnostic potential. It is anticipated to emerge as one of the novel diagnostic biomarkers for gastric cancer, albeit with relatively low specificity. The objective of this study is to investigate the potential of ZC3H13 in gastric juice as an early diagnostic biomarker for gastric cancer by assessing its expression levels in patients with various gastric diseases.\u003c/p\u003e\u003c/li\u003e\u003c/ul\u003e\u003c/p\u003e"},{"header":"2 Data and Methods","content":"\u003cp\u003e2.1 Case Data\u003c/p\u003e\u003cp\u003eBetween March 2023 and March 2024, 63 patients who underwent electronic gastroscopy at the 940 Hospital of the Joint Service Support Force of the Chinese People's Liberation Army and Liangzhou Hospital of Wuwei City and were definitively diagnosed with gastric cancer through pathology were selected as the experimental group. The control group consisted of 29 patients with gastric ulcers, 12 with chronic atrophic gastritis, and 22 with chronic non-atrophic gastritis who also underwent electronic gastroscopy during the same period. Gastric juice samples and clinical data from these patients were collected.\u003c/p\u003e\u003cp\u003eTumor clinical stages were assessed according to Tumor-Node-Metastasis (TNM) staging system (8th ed.).\u003c/p\u003e\u003cp\u003e2.2 Reagents\u003c/p\u003e\u003cp\u003eThe ZC3H13 ELISA kit was purchased from Jiangsu Enzyme Labeling Biotechnology Co.Ltd. in China.\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003e2.3 Specimen Preparation\u003c/h2\u003e\u003cp\u003eGastric juice samples (10 ml each) from patients with gastric cancer, gastric ulcer, chronic atrophic gastritis, and chronic non-atrophic gastritis were collected through electronic gastroscopy examination, centrifuged at 3000 r/min for 10 minutes, and the supernatant was taken and stored in a -80\u0026deg;C freezer for future use.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec4\" class=\"Section2\"\u003e\u003ch2\u003e2.4 Detection of ZC3H13 Protein in Gastric Juice\u003c/h2\u003e\u003cp\u003eAn enzyme-linked immunosorbent assay (ELISA) was used for detection with the ZC3H13 kit, with a correlation coefficient R\u0026thinsp;\u0026ge;\u0026thinsp;0.99; the detection range is 1.0\u0026thinsp;~\u0026thinsp;160 ng/mL; the minimum detectable concentration is less than 1.0 ng/mL. Strict adherence to the reagent kit instructions is necessary for operation. The absorbance (OD value) of each well was measured sequentially at a wavelength of 450 nm using an ELISA reader.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec5\" class=\"Section2\"\u003e\u003ch2\u003e2.5 Statistical Methods\u003c/h2\u003e\u003cp\u003eConduct statistical analysis and create plots using SPSS 25.0 and GraphPad Prism 8. The expression level of ZC3H13 in normally distributed quantitative data is presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (x\u0026thinsp;\u0026plusmn;\u0026thinsp;s), and one-way analysis of variance is employed for intergroup comparisons. Count data, including gender, tumor location, and differentiation degree, are presented as n (%), and group comparisons are conducted using a chi-square (\u003cem\u003eχ\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e) test. Receiver operating characteristic (ROC) curves are utilized to evaluate the diagnostic value of gastric juice ZC3H13 for gastric cancer and early gastric cancer, as well as the diagnostic value of combined detection of gastric juice ZC3H13 and carcinoembryonic antigen (CEA) for gastric cancer.\u003c/p\u003e\u003c/div\u003e"},{"header":"3 Results","content":"\u003cp\u003e3.1 Analysis of Gastric Juice ZC3H13 Expression Levels in Gastric Cancer Patients and Benign Stomach Disease Patients\u003c/p\u003e\u003cp\u003eThe ELISA method was employed to assess the expression level of gastric juice ZC3H13 in patients with gastric cancer and those with benign stomach diseases. The findings indicated that the expression level of gastric juice ZC3H13 in patients with gastric cancer (1.80\u0026thinsp;\u0026plusmn;\u0026thinsp;0.28) was notably lower than that of patients with gastric ulcers (2.54\u0026thinsp;\u0026plusmn;\u0026thinsp;0.23), chronic atrophic gastritis (2.36\u0026thinsp;\u0026plusmn;\u0026thinsp;0.25), and chronic non-atrophic gastritis (2.30\u0026thinsp;\u0026plusmn;\u0026thinsp;0.23). The difference was statistically significant (F\u0026thinsp;=\u0026thinsp;65.452, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001). However, there was no significant difference in the concentration of gastric juice ZC3H13 among patients with gastric ulcers, chronic atrophic gastritis, and chronic non-atrophic gastritis, as depicted in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e\u003ch2\u003e3.2 Diagnostic Efficacy of Gastric Juice ZC3H13 for Gastric Cancer\u003c/h2\u003e\u003cp\u003eTo further evaluate the efficacy of gastric juice ZC3H13 in diagnosing gastric cancer, an ROC curve was constructed for analysis. The results indicated that at a concentration of 2.12 ng/mL of gastric juice ZC3H13, the area under the curve (AUC) for differentiating between patients with gastric cancer and those without was 0.933 [95% confidence interval (CI): 0.888\u0026ndash;0.977], with a sensitivity of 88.9% and a specificity of 90.5%. For more details, refer to Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003e3.3 Diagnostic Value of Combined Gastric Juice ZC3H13 and CEA\u003c/h2\u003e\u003cp\u003eFurther research had revealed that the combination of gastric juice ZC3H13 and the traditional serum tumor marker CEA enhances the diagnostic efficacy for gastric cancer. The AUC value of the constructed ROC curve was 0.958 (95% CI, 0.925\u0026ndash;0.991), with a sensitivity of 89.2% and a specificity of 96.8%. For further details, refer to Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e\u003ch2\u003e3.4 Diagnostic Efficacy of Gastric Juice ZC3H13 for Early Gastric Cancer\u003c/h2\u003e\u003cp\u003e To investigate the potential of gastric juice ZC3H13 in diagnosing early gastric cancer, patients were categorized into two groups: early gastric cancer (TNM stage I), locally advanced gastric cancer and advanced gastric cancer (TNM stages II-IV). The findings indicated that the expression level of gastric juice ZC3H13 was significantly elevated in early gastric cancer compared to locally advanced and advanced gastric cancer (t\u0026thinsp;=\u0026thinsp;3.051, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003), as shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003ea. The AUC was 0.784 (95% CI 0.670\u0026ndash;0.898), the sensitivity and specificity were both 76.2% (refer to Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003eb).\u003c/p\u003e\u003cp\u003e3.5 Correlation Analysis Between the Expression of Gastric Juice ZC3H13 and the Clinical Pathological Characteristics of Gastric Cancer Patients\u003c/p\u003e\u003cp\u003eA study investigating the correlation between gastric juice ZC3H13 and the clinical pathological characteristics of gastric cancer patients revealed that gastric juice ZC3H13 levels were associated with tumor infiltration depth, lymph node metastasis, distant metastasis, TNM staging, and CEA levels ((\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). However, no significant correlation was found with patient gender, age, tumor location, or differentiation degree (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e\u003cp\u003eTab.1 Correlation analysis between gastric juice ZC3H13 expression level and clinical pathological characteristics of gastric cancer patients\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"91%\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 36px;\"\u003e\n \u003cp\u003eClinicopathological features\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 18px;\"\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22px;\"\u003e\n \u003cp\u003eZC3H13\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 10px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026chi;\u003csup\u003e2\u0026nbsp;\u003c/sup\u003e\u003c/em\u003e/F\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 11px;\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 36px;\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e23 (36.5)\u003c/p\u003e\n \u003cp\u003e40 (63.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.85\u0026plusmn;0.32\u003c/p\u003e\n \u003cp\u003e1.77\u0026plusmn;0.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.949\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.342\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 36px;\"\u003e\n \u003cp\u003eAge (year)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e＜60\u003c/p\u003e\n \u003cp\u003e\u0026ge;60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e21 (33.3)\u003c/p\u003e\n \u003cp\u003e42 (66.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.77\u0026plusmn;0.27\u003c/p\u003e\n \u003cp\u003e1.82\u0026plusmn;0.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.627\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.531\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 36px;\"\u003e\n \u003cp\u003eSmoking\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e40 (63.5)\u003c/p\u003e\n \u003cp\u003e23 (36.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.82\u0026plusmn;0.30\u003c/p\u003e\n \u003cp\u003e1.76\u0026plusmn;0.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.928\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.353\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 36px;\"\u003e\n \u003cp\u003eDrinking\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e48 (76.2)\u003c/p\u003e\n \u003cp\u003e15 (23.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.82\u0026plusmn;0.28\u003c/p\u003e\n \u003cp\u003e1.73\u0026plusmn;0.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e1.194\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.232\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 36px;\"\u003e\n \u003cp\u003eTumor location\u003c/p\u003e\n \u003cp\u003eGastric cardia and fundus\u003c/p\u003e\n \u003cp\u003eGastric body\u003c/p\u003e\n \u003cp\u003eGastric antrum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e11 (17.7)\u003c/p\u003e\n \u003cp\u003e26 (41.9)\u003c/p\u003e\n \u003cp\u003e25 (40.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.76\u0026plusmn;0.26\u003c/p\u003e\n \u003cp\u003e1.79\u0026plusmn;0.23\u003c/p\u003e\n \u003cp\u003e1.82\u0026plusmn;0.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.125\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.940\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 36px;\"\u003e\n \u003cp\u003eDifferentiation\u003c/p\u003e\n \u003cp\u003eHigh\u003c/p\u003e\n \u003cp\u003eModerate\u003c/p\u003e\n \u003cp\u003eLow\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e15 (23.8)\u003c/p\u003e\n \u003cp\u003e19 (30.2)\u003c/p\u003e\n \u003cp\u003e29 (46.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.93\u0026plusmn;0.33\u003c/p\u003e\n \u003cp\u003e1.80\u0026plusmn;0.30\u003c/p\u003e\n \u003cp\u003e1.73\u0026plusmn;0.21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e3.661\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.160\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 36px;\"\u003e\n \u003cp\u003eInvasion depth\u003c/p\u003e\n \u003cp\u003eT1\u003c/p\u003e\n \u003cp\u003eT2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e21 (33.3)\u003c/p\u003e\n \u003cp\u003e16 (25.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.94\u0026plusmn;0.25\u003c/p\u003e\n \u003cp\u003e1.82\u0026plusmn;0.32\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e12.357\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.006\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 36px;\"\u003e\n \u003cp\u003eT3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e10 (15.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e1.66\u0026plusmn;0.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 36px;\"\u003e\n \u003cp\u003eT4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e16 (25.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e1.68\u0026plusmn;0.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 36px;\"\u003e\n \u003cp\u003eLymph node metastasis\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e28 (44.4)\u003c/p\u003e\n \u003cp\u003e35 (55.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.92\u0026plusmn;0.28\u003c/p\u003e\n \u003cp\u003e1.70\u0026plusmn;0.24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e3.205\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 36px;\"\u003e\n \u003cp\u003eDistant metastases\u003c/p\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e51 (81.0)\u003c/p\u003e\n \u003cp\u003e12 (19.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.85\u0026plusmn;0.28\u003c/p\u003e\n \u003cp\u003e1.60\u0026plusmn;0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e2.748\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.006\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 36px;\"\u003e\n \u003cp\u003eTNM stage\u003c/p\u003e\n \u003cp\u003eⅠ\u003c/p\u003e\n \u003cp\u003eⅡ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e24 (38.1)\u003c/p\u003e\n \u003cp\u003e11 (17.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.96\u0026plusmn;0.27\u003c/p\u003e\n \u003cp\u003e1.79\u0026plusmn;0.28\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e16.565\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 36px;\"\u003e\n \u003cp\u003eⅢ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e16 (25.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e1.71\u0026plusmn;0.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 36px;\"\u003e\n \u003cp\u003eⅣ\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e12 (19.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e1.60\u0026plusmn;0.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 36px;\"\u003e\n \u003cp\u003eCEA (\u0026mu;g/L)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e＜5\u003c/p\u003e\n \u003cp\u003e\u0026ge;5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e51 (81.0)\u003c/p\u003e\n \u003cp\u003e12 (19.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.84\u0026plusmn;0.28\u003c/p\u003e\n \u003cp\u003e1.62\u0026plusmn;0.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e2.599\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.009\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 36px;\"\u003e\n \u003cp\u003eCA 199 (\u0026mu;g/L)\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e＜37\u003c/p\u003e\n \u003cp\u003e\u0026ge;37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 18px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e51 (81.0)\u003c/p\u003e\n \u003cp\u003e12 (19.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 22px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e1.82\u0026plusmn;0.26\u003c/p\u003e\n \u003cp\u003e1.76\u0026plusmn;0.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 10px;\"\u003e\n \u003cp\u003e0.919\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 11px;\"\u003e\n \u003cp\u003e0.358\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"4 Discussion","content":"\u003cp\u003eIn recent years, m6A methylation modification has been confirmed as a key regulatory mechanism in gastric cancer[\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. ZC3H13, a type of m6A methyltransferase, plays a crucial role in the occurrence and development of tumors[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Some studies have found that ZC3H13 may participate in the occurrence and development of various tumors as either a pro-cancer or anti-cancer factor. For instance, a study by Zhu et al[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] found that ZC3H13 is downregulated in colorectal cancer tissues, suggesting that it can act as an anti-cancer factor to inhibit the proliferation and invasion of rectal cancer. Its mechanism may be related to the inactivation of the Ras-ERK signaling pathway. Xie et al[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] observed that ZC3H13 is expressed at low levels in papillary thyroid carcinoma cell lines. Further investigation revealed that ZC3H13 inhibits the growth of papillary thyroid carcinoma by mediating the m6A modification-induced degradation of GTPase activating protein 1 (IQGAP1) containing IQ motifs. Wang et al[\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] monitored the expression of ZC3H13 in liver cancer and adjacent normal tissues, noting that ZC3H13 was downregulated in liver cancer tissues. Through m6A-PKM2-mediated glycolysis, ZC3H13 inhibited the progression of liver cancer and increased the sensitivity of liver cancer cells to cisplatin. In the context of gastric cancer, researchers have found that ZC3H13 is involved in the occurrence and development of the disease[\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. For example, McGrail et al[\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] observed that the expression level of ZC3H13 in gastric cancer tissue was significantly increased. ZC3H13 silencing can inhibit the proliferation, migration, and invasion ability of gastric cancer cells, although the specific molecular mechanism remains unclear.\u003c/p\u003e\u003cp\u003eOur research group has previously discovered that the ZC3H13 protein is highly expressed in blood and tissues, and it has the potential to serve as a diagnostic biomarker for gastric cancer. However, its specificity is relatively low[\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] at 50%. Gastric juice is secreted directly by the gastric mucosa and contains numerous shed tumor cells and tumor metabolism-related substances. Moreover, the contents of gastric juice are dynamically changing, with the composition and biomarkers varying with the disease state. By collecting and analyzing gastric juice, lesions or abnormalities that might be missed during endoscopic examination can be detected[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Furthermore, real-time monitoring of biomarker changes in gastric juice can provide valuable insights into disease progression, treatment response, and overall management of gastric cancer patients, facilitating personalized treatment goals[\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eCurrently, researchers have isolated extracellular vesicles, long non-coding RNAs, DNA, and proteins from gastric juice. They have found that liquid biopsy techniques using gastric juice as the detection sample exhibit higher sensitivity and specificity compared to those using blood, and they better represent the heterogeneity of gastric cancer[\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Zhou et al[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e] studied 66 gastric cancer patients and 66 healthy individuals, using qRT-PCR to measure the expression of piR-1245 in gastric juice and tissues. The results indicated that the level of piR-1245 in the gastric juice of gastric cancer patients was significantly higher than in healthy individuals (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.01), and the expression of piR-1245 in gastric juice and tissues was consistent. Gastric juice piR-1245 can differentiate gastric cancer patients from healthy individuals, with an AUC value of 0.885, surpassing CEA (AUC value of 0.642) and CA724 (AUC value of 0.673). Another study found that H19[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] and miR-92a\u0026minus;3p[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e] in gastric juice are not only closely related to the diagnosis of gastric cancer but also that their expression levels correlate with the classification and staging of gastric cancer, making them potential prognostic markers for the disease.\u003c/p\u003e\u003cp\u003eThis study initially detected the expression of gastric juice ZC3H13 in the patients with gastric cancer, gastric ulcer, chronic atrophic gastritis, and chronic non-atrophic gastritis. We found that the expression level of gastric juice ZC3H13 in the gastric cancer patients was lower than that of patients with gastric ulcers, chronic atrophic gastritis, and chronic non-atrophic gastritis. However, there was no significant difference in the expression level of gastric juice ZC3H13 in the patients with gastric ulcers, chronic atrophic gastritis, and chronic non-atrophic gastritis. The ROC curve results for gastric juice ZC3H13 in diagnosing gastric cancer showed that the sensitivity and specificity of gastric juice ZC3H13 in distinguishing gastric cancer patients from non-gastric cancer patients were 88.9% and 90.5%, respectively, indicating high clinical value. Meanwhile, the sensitivity and specificity of the combination of gastric juice ZC3H13 and the traditional tumor marker CEA in diagnosing gastric cancer were 89.2% and 96.8%, respectively, suggesting that gastric juice ZC3H13 is closely related to gastric cancer and has the potential to serve as a diagnostic marker for the disease.\u003c/p\u003e\u003cp\u003eOur research group previously discovered that the ZC3H13 protein is highly expressed in blood and tissues. However, this study indicates that the expression level of ZC3H13 is reduced in the gastric juice of gastric cancer patients, which contradicts earlier findings. The discrepancy between the protein expression levels in gastric juice and those in tissues and blood warrants our attention and necessitates further investigation to understand the underlying causes. Similar observations have been made in other studies. In 2013, Cui et al[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e] utilized real-time quantitative reverse transcription polymerase chain reaction to determine that the expression levels of circulating miR-21 and miR-106a in the gastric juice of gastric cancer patients were significantly lower than those in patients with benign gastric diseases. Conversely, gastric mucosal biopsy results indicated that the expression levels of circulating miR-21 and miR-106a were elevated in the plasma and tissues of gastric cancer patients. Shao et al[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e] conducted another study where they examined the expression levels of hsa_circ_0065149 in the gastric juice of gastric cancer patients, chronic atrophic gastritis patients, gastric ulcer patients, and healthy volunteers. They also observed inconsistencies between the expression levels in gastric juice and those in plasma and tissue. They suggest that this contrasting trend may be associated with the function of exosomes.\u003c/p\u003e\u003cp\u003eThe poor prognosis of gastric cancer is largely attributed to the absence of highly sensitive and specific early diagnostic strategies. Endoscopy remains the primary method for diagnosing early gastric cancer, but its invasiveness and high cost restrict its use for screening purposes. Traditional blood markers such as CEA, CA199, and pepsinogen have extremely low diagnostic value for early gastric cancer[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Liquid biopsy is a novel technique that has the potential to improve the early diagnosis rate of gastric cancer. However, due to the limited number of components in the body fluids of patients with early gastric cancer, the detection rate is low, and the application of liquid biopsy for gastric cancer screening and early diagnosis still faces challenges. Hee et al[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e] analyzed the levels of microbial-derived extracellular vesicles (EVs) in the gastric juice and other body fluids of patients with low-grade dysplasia, high-grade dysplasia, and gastric cancer. The study found that as the disease progressed, the microbial diversity in gastric juice and serum samples significantly changed. In gastric juice, the abundance of C. acnes and S. oralis showed a significant increase with the progression of disease severity. These findings underscore the potential of microbial-derived EVs as early diagnostic tools for gastric cancer and its precursors. Wang et al[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] used ELISA to detect the levels of aldehyde dehydrogenase 1 and gastrin 17 in the gastric juice of patients with various gastric diseases. The research results indicated that the levels of aldehyde dehydrogenase 1 and gastrin 17 in the gastric juice of gastric cancer patients were higher than those of patients with gastric ulcers and gastritis. Additionally, the levels of these markers in gastric ulcer patients were higher than those in gastritis patients. The AUC values for aldehyde dehydrogenase 1, gastrin 17, and the combination of both markers in gastric juice for the diagnosis of gastric cancer were 0.695, 0.759, and 0.792, respectively. Our study found that the area under the ROC curve for gastric juice ZC3H13 in distinguishing early gastric cancer from advanced gastric cancer was 0.784, with a sensitivity of 76.2% and a specificity of 76.2%. This result suggests that gastric juice ZC3H13 has certain reference value for the diagnosis of early gastric cancer and may offer a new strategy for the early screening of gastric cancer.\u003c/p\u003e\u003cp\u003eThis study also found that the expression level of gastric juice ZC3H13 is closely related to the clinical and pathological characteristics of gastric cancer patients, such as tumor infiltration depth, lymph node metastasis, distant metastasis, and TNM staging, further confirming the important role of gastric juice ZC3H13 in the progression of gastric cancer.\u003c/p\u003e\u003cp\u003eAlthough this study has achieved certain results, there are still some limitations. For instance, the relatively small sample size included in this study may affect the stability and reliability of the results. In the future, we plan to expand the sample size and conduct multicenter, prospective studies to validate the clinical value of gastric juice ZC3H13 as a diagnostic biomarker for gastric cancer. Simultaneously, we will also explore the specific molecular mechanisms and trends of gastric juice ZC3H13 in the occurrence and development of gastric cancer, providing new targets and treatment strategies for the treatment of gastric cancer.\u003c/p\u003e"},{"header":"5 Conclusion","content":"\u003cp\u003eGastric juice ZC3H13, as a potential diagnostic biomarker for gastric cancer, has high sensitivity and specificity and is expected to become an important tool for early screening and diagnosis of gastric cancer. In the future, we will continue to conduct in-depth research on the diagnostic value and therapeutic potential of gastric juice ZC3H13 in gastric cancer, contributing more to the prevention and treatment of gastric cancer.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003ch2\u003eConsent to publish\u003c/h2\u003e\u003cp\u003e All authors read and approved to publish the final manuscript.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003ch2\u003eCompeting interests\u003c/h2\u003e\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e\u003cp\u003eWuwei Science and Technology Bureau (project number WW24B01SF087).\u003c/p\u003e\u003cp\u003eData availability\u003c/p\u003e\u003cp\u003eData supporting the findings of this study are available from the corresponding author upon reasonable request.\u003c/p\u003e\u003cp\u003eEthics approval and Consent to participate\u003c/p\u003e\u003cp\u003eThis study was approved by the Ethics Committee of 940th Hospital of Joint Logistics Support Force of People's Liberation Army (No. 2023KYLL345) and was performed in accordance with the ethical standards described in the Declaration of Helsinki. Informed consent for this study was obtained using the opt-out system with the approval of the ethics committee.\u003c/p\u003e\u003cp\u003eConsent to participate\u003c/p\u003e\u003cp\u003eInformed consent was obtained from the participants to participate in the current study.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eXZ Wei and YH Liu designed the study. ZJ Zhang performed the work and drafted the manuscript, QY Liu, Y Zhu, QQ Yang, KC Zhang, AF Duo and SS Ding collection and interpretation of specimen data and refined the drafted manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2024,74(3):229-263.\u003c/li\u003e\n\u003cli\u003eSmyth E C, Nilsson M, Grabsch H I, et al. Gastric cancer[J]. Lancet, 2020,396(10251):635-648.\u003c/li\u003e\n\u003cli\u003eHiramatsu T, Kakushima N, Kuribara H, et al. Recent advancement in endoscopic diagnosis for risk stratification of gastric cancer[J]. Clin Endosc, 2025.\u003c/li\u003e\n\u003cli\u003eLone S N, Nisar S, Masoodi T, et al. Liquid biopsy: a step closer to transform diagnosis, prognosis and future of cancer treatments[J]. Mol Cancer, 2022,21(1):79.\u003c/li\u003e\n\u003cli\u003eWang Y, Liu H, Li X, et al. Study on the value of gastrin 17 and aldehyde dehydrogenase 1 in gastric juice for early diagnosis in gastric cancer[J]. Front Oncol, 2025,15:1521868.\u003c/li\u003e\n\u003cli\u003eGasparello J, Ceccon C, Angerilli V, et al. Liquid biopsy in gastric cancer: A snapshot of the current state of the art[J]. J Liq Biopsy, 2025,7:100288.\u003c/li\u003e\n\u003cli\u003eRoy S, Kanda M, Nomura S, et al. Diagnostic efficacy of circular RNAs as noninvasive, liquid biopsy biomarkers for early detection of gastric cancer[J]. Mol Cancer, 2022,21(1):42.\u003c/li\u003e\n\u003cli\u003eWang H, Zhang Y, Zhang H, et al. Liquid biopsy for human cancer: cancer screening, monitoring, and treatment[J]. MedComm (2020), 2024,5(6):e564.\u003c/li\u003e\n\u003cli\u003eSkryabin G, Enikeev A, Beliaeva A, et al. Distinctive Features of Extracellular Vesicles Present in the Gastric Juice of Patients with Gastric Cancer and Healthy Subjects[J]. Int J Mol Sci, 2025,26(12).\u003c/li\u003e\n\u003cli\u003eWu D, Zhang P, Ma J, et al. Serum biomarker panels for the diagnosis of gastric cancer[J]. Cancer Med, 2019,8(4):1576-1583.\u003c/li\u003e\n\u003cli\u003eHerrera-Pariente C, Montori S, Llach J, et al. Biomarkers for Gastric Cancer Screening and Early Diagnosis[J]. Biomedicines, 2021,9(10).\u003c/li\u003e\n\u003cli\u003eMeijing Z, Tianhang L, Biao Y. N6-Methyladenosine Modification Patterns and Tumor Microenvironment Immune Characteristics Associated With Clinical Prognosis Analysis in Stomach Adenocarcinoma[J]. Front Cell Dev Biol, 2022,10:913307.\u003c/li\u003e\n\u003cli\u003eHuang J, Shao Y, Gu W. Function and clinical significance of N6-methyladenosine in digestive system tumours[J]. Exp Hematol Oncol, 2021,10(1):40.\u003c/li\u003e\n\u003cli\u003eHan Y, Sun J, Yao M, et al. Biological roles of enhancer RNA m6A modification and its implications in cancer[J]. Cell Commun Signal, 2025,23(1):254.\u003c/li\u003e\n\u003cli\u003eJia LJ, Zhang YQ, Zhang BH, etc Expression and clinical significance of m~6A methyltransferase ZC3H13 in gastric cancer tissue and serum [J]. Cancer Prevention and Treatment Research, 2022, 49 (08): 792-798.\u003c/li\u003e\n\u003cli\u003eDing S Q, Zhang X P, Pei J P, et al. Role of N6-methyladenosine RNA modification in gastric cancer[J]. Cell Death Discov, 2023,9(1):241.\u003c/li\u003e\n\u003cli\u003eGao L, Gao J, He J, et al. Identification of m6A methyltransferase-related WTAP and ZC3H13 predicts immune infiltrates in glioblastoma[J]. Sci Rep, 2025,15(1):4412.\u003c/li\u003e\n\u003cli\u003eZhu D, Zhou J, Zhao J, et al. ZC3H13 suppresses colorectal cancer proliferation and invasion via inactivating Ras-ERK signaling[J]. J Cell Physiol, 2019,234(6):8899-8907.\u003c/li\u003e\n\u003cli\u003eXie R, Chen W, Lv Y, et al. Overexpressed ZC3H13 suppresses papillary thyroid carcinoma growth through m6A modification-mediated IQGAP1 degradation[J]. J Formos Med Assoc, 2023.\u003c/li\u003e\n\u003cli\u003eWang Q, Xie H, Peng H, et al. ZC3H13 Inhibits the Progression of Hepatocellular Carcinoma through m(6)A-PKM2-Mediated Glycolysis and Enhances Chemosensitivity[J]. J Oncol, 2021,2021:1328444.\u003c/li\u003e\n\u003cli\u003eMcGrail D J, Pili\u0026eacute; P G, Rashid N U, et al. High tumor mutation burden fails to predict immune checkpoint blockade response across all cancer types[J]. Ann Oncol, 2021,32(5):661-672.\u003c/li\u003e\n\u003cli\u003eLianos G D, Kyrochristou G D, Lianou A D, et al. Gastric Juice Biomarkers in Gastric Cancer: New Trends?[J]. Maedica (Bucur), 2024,19(4):775-779.\u003c/li\u003e\n\u003cli\u003eYou H S, Park J Y, Seo H, et al. Increasing correlation between oral and gastric microbiota during gastric carcinogenesis[J]. Korean J Intern Med, 2024,39(4):590-602.\u003c/li\u003e\n\u003cli\u003eOnoyama T, Ishikawa S, Isomoto H. Gastric cancer and genomics: review of literature[J]. J Gastroenterol, 2022,57(8):505-516.\u003c/li\u003e\n\u003cli\u003eSi Y T, Xiong X S, Wang J T, et al. Identification of chronic non-atrophic gastritis and intestinal metaplasia stages in the Correa\u0026apos;s cascade through machine learning analyses of SERS spectral signature of non-invasively-collected human gastric fluid samples[J]. Biosens Bioelectron, 2024,262:116530.\u003c/li\u003e\n\u003cli\u003eFel\u0026iacute;pez N, Montori S, Mendizuri N, et al. The Human Gastric Juice: A Promising Source for Gastric Cancer Biomarkers[J]. Int J Mol Sci, 2023,24(11).\u003c/li\u003e\n\u003cli\u003eZhou X, Liu J, Meng A, et al. Gastric juice piR-1245: A promising prognostic biomarker for gastric cancer[J]. J Clin Lab Anal, 2020,34(4):e23131.\u003c/li\u003e\n\u003cli\u003eChen J S, Wang Y F, Zhang X Q, et al. H19 serves as a diagnostic biomarker and up-regulation of H19 expression contributes to poor prognosis in patients with gastric cancer[J]. Neoplasma, 2016,63(2):223-230.\u003c/li\u003e\n\u003cli\u003eLiu L, Dai A, Zhang Z, et al. LncRNA PITPNA-AS1 promotes gastric cancer by increasing SOX4 expression via inhibition of miR-92a-3p[J]. Aging (Albany NY), 2021,13(17):21191-21201.\u003c/li\u003e\n\u003cli\u003eCui L, Zhang X, Ye G, et al. Gastric juice MicroRNAs as potential biomarkers for the screening of gastric cancer[J]. Cancer, 2013,119(9):1618-1626.\u003c/li\u003e\n\u003cli\u003eShao Y, Tao X, Lu R, et al. Hsa_circ_0065149 is an Indicator for Early Gastric Cancer Screening and Prognosis Prediction[J]. Pathol Oncol Res, 2020,26(3):1475-1482.\u003c/li\u003e\n\u003cli\u003eConti C B, Agnesi S, Scaravaglio M, et al. Early Gastric Cancer: Update on Prevention, Diagnosis and Treatment[J]. Int J Environ Res Public Health, 2023,20(3).\u003c/li\u003e\n\u003cli\u003eYou H S, Park J Y, Seo H, et al. Distinct microbial signatures of liquid biopsy samples during gastric carcinogenesis and insights from extracellular vesicle analysis[J]. Korean J Intern Med, 2025,40(4):571-583.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"gastric cancer, Liquid biopsy, Gastric juice, ZC3H13, M6A methyltransferase","lastPublishedDoi":"10.21203/rs.3.rs-7364885/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7364885/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e\u003cp\u003eTo investigate the expression of the m6A methyltransferase ZC3H13 in the gastric juice of patients with various gastric diseases and its potential diagnostic value for gastric cancer.\u003c/p\u003e\u003ch2\u003eMethod\u003c/h2\u003e\u003cp\u003eDetection of gastric juice ZC3H13 expression levels of 126 patients with gastric cancer, gastric ulcer, chronic atrophic gastritis, and chronic non-atrophic gastritis using ELISA. The diagnostic potential of gastric juice ZC3H13 as a biomarker for gastric cancer was evaluated by constructing receiver operating characteristic (ROC) curves. Additionally, the diagnostic efficacy of combining gastric juice ZC3H13 detection with the traditional serum biomarker carcinoembryonic antigen (CEA) for gastric cancer was further explored. Concurrently, the expression levels of gastric juice ZC3H13 were examined to assess its diagnostic capability for early-stage gastric cancer. Finally, the correlation between gastric juice ZC3H13 and the clinical pathological characteristics of gastric cancer patients was analyzed using a chi-square(\u003cem\u003eχ\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e) test.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eThe expression levels of gastric juice ZC3H13 in the patients with gastric cancer was significantly lower than that of patients with gastric ulcers, chronic atrophic gastritis, and chronic non-atrophic gastritis. Analysis of gastric cancer patients revealed that the expression level of gastric juice ZC3H13 was significantly correlated with tumor infiltration degree, lymph node metastasis, distant metastasis, and TNM staging (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The area under the ROC curve (AUC) of gastric juice ZC3H13 for diagnosing gastric cancer was 0.933, with a sensitivity of 88.9% and a specificity of 90.5%. The expression level of gastric juice ZC3H13 in the patients with early gastric cancer was higher than that of those with locally advanced and advanced gastric cancer. The AUC value for distinguishing early gastric cancer was 0.784, with a sensitivity of 76.2% and a specificity of 76.2%. The AUC value for the combined detection of gastric juice ZC3H13 and CEA for detecting gastric cancer was 0.958, with a sensitivity of 89.2% and a specificity of 96.8%.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003e Gastric juice ZC3H13 is under-expressed in gastric cancer patients, and its expression level is higher in early gastric cancer patients compared to locally advanced and advanced gastric cancer patients. This suggests that gastric juice ZC3H13 may have clinical application value in the diagnosis of gastric cancer, including early gastric cancer.\u003c/p\u003e","manuscriptTitle":"Gastric juice ZC3H13 as a potential biomarker for gastric cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-22 09:31:03","doi":"10.21203/rs.3.rs-7364885/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"15e912cc-1d27-41a8-90fb-febb7a7e5274","owner":[],"postedDate":"September 22nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-12-10T11:39:19+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-22 09:31:03","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7364885","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7364885","identity":"rs-7364885","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}