Association of preoperative low circulating basophil counts with the prognostic factor in gastric cancer

Association of preoperative low circulating basophil counts with the prognostic factor in 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 Association of preoperative low circulating basophil counts with the prognostic factor in gastric cancer Makiko Kawano, Yoko Oshima, fumiaki Shiratori, Takashi Suzuki, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5011542/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 27 Jan, 2025 Read the published version in Journal of Gastrointestinal Cancer → Version 1 posted 9 You are reading this latest preprint version Abstract Purpose Basophils play a crucial role in immunoglobulin E-mediated allergic reactions and parasitic infections. Recently, a low basophil count was reported to be a poor prognostic indicator in patients with malignant tumors. This study aimed to investigate the cut-off value to evaluate the clinicopathological and prognostic significance of the basophil count in patients with gastric cancer. Methods This study enrolled 1192 consecutive gastric cancer surgically treated between 2001 and 2020. The cut-off values were fixed at 26/µl based on the receiver of characteristics curves for overall survival, and 606 patients were classified as the low basophil group. The clinicopathological and prognostic significance of the low basophil count was assessed by univariate and multivariate analyses Results Elderly age ( p = 0.009), high C-reactive protein level ( p < 0.001), and low neutrophil count ( p < 0.001), are independently associated with low basophil count. The low basophil group demonstrated a significantly worse overall survival than the high basophil group ( p = 0.005). Although there was no significant difference in stage I, the low basophil group demonstrated poor overall survival in stage II/III/IV. The low basophil count was an independent risk factor for poor overall survival ( p = 0.042). Conclusion Low basophil count was significantly associated with elderly age, high C-reactive protein level, and low neutrophil count (< 26/µl). And, low basophil count was an independent poor prognostic factor in patients with gastric cancer. Thus, preoperative circulating basophil count assessment may be useful for predicting the postoperative survival of patients with gastric cancer. Gastric cancer Basophil count Prognosis Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Gastric cancer is the fourth and third leading cause of death globally and in Japan, accounting for approximately 800,000 and 40,000 deaths annually, respectively [ 1 , 2 ]. Several studies reported the association between neutrophils, lymphocytes, and C-reactive protein (CRP) in gastric cancer [ 3 – 5 ]. A high neutrophil-to-lymphocyte ratio [ 6 , 7 ], high CRP level [ 3 , 8 ], and low lymphocyte count are considered poor prognostic factors [ 4 ], and an association between these factors and tumor growth and progression has been indicated. However, the fraction of basophils is very small; thus, only one study [ 9 ] reported on the clinicopathological significance of basophils in patients with gastric cancer. Basophil is a type of granulocyte and accounts for < 1% of white blood cells in peripheral blood. Basophil is involved in allergic diseases and parasitic infections by regulating immunoglobulin E -mediated reactions and type 2 immune responses through various mediators, including histamine, leukotriene C4, and interleukin-4 and − 13 [ 10 ]. Clinicopathological significance of circulating basophils in esophageal cancer [ 11 ], gastric cancer [ 9 ], and colorectal cancer [ 12 – 14 ] have been reported in gastrointestinal cancer. These previous studies revealed that low circulating basophil count was associated with poor prognosis other than gastric cancer. These reports analyzed mixed populations, including both surgical and non-surgical cases, and only one report focused on surgical cases [ 11 ]. Wu C et al. discussed that the high basophil count around the tumor cells was associated with poor prognosis in advanced and/or recurrent gastric cancer [ 9 ]. Such tendency was not similar in esophageal cancer [ 11 ] and colorectal cancer [ 12 – 14 ]. No studies analyzed the association between circulating basophil count and prognosis only focused on surgically treated gastric cancer. Therefore, this study analyzed the clinicopathological and prognostic significance of preoperative circulating basophil count in patients with surgically treated gastric cancer to establish the cut-off value of basophil count as a derivation cohort. Methods Study population A total of 1514 patients with primary gastric cancer underwent surgery at Toho University Omori Medical Center from January 2001 to December 2020. This retrospective study enrolled 1192 consecutive patients (811 males and 381 females with a median age of 68 years; range, 32–96 years) after excluding patients who received preoperative chemotherapy, those who had residual gastric cancer, and double cancer (Fig. 1 ). The cut-off value was determined to classify circulating basophil count as low group and high group based on receiving operating characteristic curves, and then clinicopathological factors and overall prognosis were compared between these two groups. All patients were followed up until the end of December 2020 or death. The median follow-up period was 48 (range: 0–60) months. The Ethics Committee of Toho University Omori Medical Center (#M23174 21320 21039 20200 20196 19056 18002) approved this study, conducted under the Declaration of Helsinki. Informed consent was obtained in the form of opt-out on the web-site. Those who rejected were excluded. Circulating basophil count and pathological factors We analyzed circulating basophil count through routine blood tests within 7 days preoperatively. The tumor, node, and metastasis stage [ 15 ] were determined by pathological diagnosis using resected specimens. Correlation between basophil count and clinicopathological factors, such as age, gender, tumor depth, lymph node metastasis, distant metastasis, liver metastasis, CRP, lymphocyte count, and neutrophil count, were evaluated. Tumor depth was classified into the T1T2 (M, SM) and T3T4 (MP, SS, SE, SI) groups. Lymph node, distant, and liver metastases were classified as negative or positive. Statistical analysis The cut-off value of basophil count was set at 26/µl based on receiving operating characteristic curves for overall survival (Fig. 2 a). Univariate and multivariate analyses were performed to evaluate the clinicopathological and prognostic significance of low basophil count. The p -value was calculated using Fisher’s exact test for univariate analysis. Overall survival probabilities were calculated using the product limit method of Kaplan–Meier, considering overall deaths and the log-rank test was utilized to analyze the survival differences between the groups. The multivariate analysis calculated the odds ratio, 95% confidence interval, and p -value using a logistic regression analysis. EZR was used for all statistical analyses [ 16 ]. Two-sided p -values of < 0.05 indicated statistical significance. Results The median basophil count of 1192 patients was 27/µl (0–368/µl). We fixed the cut-off value of the basophil count as 26/µl based on the receiving operating characteristic analysis(Fig. 2 a). We classified 586 (49.2%) patients into the high basophil group and 606 (50.8%) patients into the low basophil group using the cut-off value (Fig. 2 b). Clinicopathological significance of low basophil count Univariate analysis identified elderly age ( p < 0.001), high CRP ( p < 0.001), low lymphocyte count ( p = 0.002), and low neutrophil count ( p = 0.002) to be significantly associated with low basophil count (Table 1). Multivariate analysis determined elderly age ( p = 0.009), high CRP ( p < 0.001), and low neutrophil count ( p < 0.001) to be significantly associated with low basophil count (Table 2). Prognostic significance of low basophil count on overall survival Univariate analysis of all patients revealed a significantly worse prognosis of the low basophil group than that of the high basophil group ( p = 0.005, Fig. 3 ). The prognosis of both groups was almost similar, comparing the prognosis of both groups according to the stage, in stage I. However, the low basophil group demonstrated a worse prognosis than the high basophil group in stage II/III/IV (Fig. 4 ). Univariate and multivariate analyses of the prognostic effect of low basophil count on overall survival Univariate analysis revealed that elderly age ( p < 0.001), T3T4 invasion depth ( p < 0.001), lymph node metastasis ( p < 0.001), distant metastasis ( p < 0.001), liver metastasis ( p < 0.001), high CRP ( p < 0.001), low lymphocytes ( p < 0.001), low neutrophils ( p < 0.001), and low basophil count ( p = 0.005) were significantly associated with poor overall survival. Multivariate analysis determined elderly age ( p = 0.001), T3T4 invasion depth ( p < 0.001), lymph node metastasis ( p < 0.001), high CRP ( p < 0.001), low lymphocyte count ( p = 0.039), high neutrophil count ( p = 0.028), and low basophil count ( p = 0.042) as independent risk factors for poor overall survival (Table 3). Discussion No study indicated the cut-off value of circulating basophil count in gastric cancer; thus, this study aimed to establish an appropriate cut-off value (< 26/µl) as the derivation cohort. We assessed the clinicopathological significance of preoperative circulating basophil count in surgically treated gastric cancer. Additionally, we revealed that low basophil count was associated with tumor progression. The low basophil count was an independent risk factor for poor overall survival. This study is the first to reveal an association between preoperative circulating basophil count and prognosis in surgically treated gastric cancer. Other similar studies, indicated cut-off values for circulating basophil count at 25/µl (area under the curve = 0.669) in colorectal cancer [ 13 ] and 20/µl (area under the curve = 0.7208) in unresectable gastric cancer [ 9 ] based on receiver operating characteristic curves. This value was similar to the cut-off value set in our present study, so the cut-off value might be reasonable. Peripheral blood cell count studies revealed low lymphocyte count [ 4 ] and high neutrophil count [ 17 ] as risk factors for poor prognosis in gastric cancer. Since basophils are negatively correlated with neutrophils, it is natural that low basophil counts are a poor prognostic factor. Our study revealed that low lymphocyte count, high neutrophil count, and low basophil count were independent poor prognostic factors. A significant correlation between low basophil, low lymphocyte, and neutrophil count was observed, which may reflect decreased hematopoietic function mainly due to aging. A significant correlation between low basophil count and high CRP level was observed because differentiation into neutrophils is prioritized during infiltration that causes high CRP levels, such as inflammation or infection. The immunohistochemical analysis of previous reports revealed that a large number of basophils infiltrating the tumor was a poor prognostic factor in gastric cancer [ 9 , 18 ]. Furthermore, it has been reported that there is a positive correlation between the infiltration of basophils into the tumor and the infiltration of M2 macrophages into the tumor in gastric cancer. Macrophages are known to promote tumor angiogenesis and distant metastasis [ 19 , 20 ], suggesting that basophils may also be immunologically involved in the tumor microenvironment in gastric cancer. There are only limited reports on the relationship between the number of basophils in peripheral blood and the number of basophils infiltrating into the tumor, and it is not yet fully understood. Chronic urticaria is a typical disease in which the number of basophils in the peripheral blood decreases. In patients with chronic urticaria, the number of basophils in the peripheral blood decreases as basophils are recruited to the skin, which is the main site of inflammation. [ 21 ] Considering the biological response of patients with chronic urticaria, gastric cancer patients may also similarly decrease the number of circulating basophils due to an increase in the number of basophils infiltrating the tumor. Regarding the prognosis in unresectable gastric cancer who were treated with immunotherapy, the high basophil group demonstrated a worse prognosis than the low basophil group [ 9 ]. This contradicts our study results probably because the research participants were limited to recurrence and distant metastasis cases [ 9 ]. The prognosis of the high and low basophil count groups was very similar in stage I. This indicates that the low basophil counts did not have any effects on the other cause of death in stage I. The absence of a statistically significant difference in stage III/IV was due to the insufficient number of cases. This study has some limitations. First, this is a retrospective single-center study. Second, this study did not investigate the patient’s history of immune diseases, vulnerabilities including bone marrow function, allergies, or use of immune-related drugs, including anti-allergy drugs and/or steroids. Third, this study included long periods of patients; thus, various adjuvant chemotherapy and systematic therapy after recurrence influenced the prognosis. The present study was a derivation cohort to fix the appropriate cut-off value of circulating basophil count. Further evaluation cohort is warranted to ensure the impact of circulating basophil count. Therefore, further multi-institutional studies are required to assess the effect of low circulating basophil counts on the survivals in patients with gastric cancer postoperatively. In conclusion, low basophil count was significantly associated with high neutrophil count and high CRP level, but low basophil count was an independent poor prognostic factor in patients with gastric cancer. Thus, preoperative circulating basophil count assessment may be useful for predicting the postoperative survival of patients with gastric cancer. Declarations Acknowledgments The authors would like to thank MARUZEN-YUSHODO Co., Ltd. (https://kw.maruzen.co.jp/kousei-honyaku/) for the English language editing. We thank Seiko Otsuka for preparing the ethical documents. Funding The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Competing Interests The authors have no relevant financial or non-financial interests to disclose. Author Contributions Makiko Kawano, Hideaki Shimada, and Kimihiko Funahashi conceived and designed the current study. Makiko Kawano, Yoko Oshima, Fumiaki Shiratori, Takashi Suzuki, and Satoshi Yajima contributed to the acquisition of the patient’s clinicopathological data. Makiko Kawano and Yoko Oshima analyzed the patient data. Makiko Kawano and Hideaki Shimada drafted the manuscript. All authors read and approved the final manuscript. Ethical approval This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Faculty of Medicine, Toho University Omori Medical Center (Tokyo, Japan; #M23174 21320 21039 20200 20196 19056 18002). Consent to participate The participants were given the opportunity to decline to be enrolled in the study (opt-out). 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Intern Med J. 45:854-859. https://doi.org/10.1111/imj.12786 He X, Cao Y, Gu Y, Fang H, Wang J, Liu X, Lv K et al (2021) Clinical Outcomes and Immune Metrics in Intratumoral Basophil-Enriched Gastric Cancer Patients. Ann Surg Oncol. 28:6439-6450. https://doi.org/10.1245/s10434-021-09815-0 Lewis CE, Harney AS, Pollard JW (2016) The Multifaceted Role of Perivascular Macrophages in Tumors. Cancer Cell. 30(1):18-25. https://doi.org/10.1016/j.ccell.2016.05.017 Zheng Z, Jia S, Shao C, Shi Y (2020) Irradiation induces cancer lung metastasis through activation of the cGAS-STING-CCL5 pathway in mesenchymal stromal cells. Cell Death Dis. 7;11(5):326. https://doi.org/10.1038%2Fs41419-020-2546-5 Saini S.S. (2023) Urticaria and basophils. Allergol Int. 72:369-374. https://doi.org/10.1016/j.alit.2023.05.001 Tables Tables are available in the Supplementary Files section. Additional Declarations No competing interests reported. Supplementary Files Tables.pdf Cite Share Download PDF Status: Published Journal Publication published 27 Jan, 2025 Read the published version in Journal of Gastrointestinal Cancer → Version 1 posted Editorial decision: Revision requested 27 Sep, 2024 Reviews received at journal 25 Sep, 2024 Reviews received at journal 09 Sep, 2024 Reviewers agreed at journal 09 Sep, 2024 Reviewers agreed at journal 03 Sep, 2024 Reviewers invited by journal 01 Sep, 2024 Editor assigned by journal 01 Sep, 2024 Submission checks completed at journal 01 Sep, 2024 First submitted to journal 01 Sep, 2024 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. 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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-5011542","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":359801325,"identity":"48d33bd0-6ff2-4218-9a71-692b3d3310f4","order_by":0,"name":"Makiko Kawano","email":"","orcid":"","institution":"Department of Gastroenterological Surgery, Toho University Omori Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Makiko","middleName":"","lastName":"Kawano","suffix":""},{"id":359801327,"identity":"7cd3bf30-113b-490b-bed4-0d39ff8e12b5","order_by":1,"name":"Yoko Oshima","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9klEQVRIiWNgGAWjYFACHoYDDAw2QEYCAwNjA0KUkJY0kBbGBqK1AMFhdC14AD//2YOHbtScj+ZnT2B/8HGHDYPBAeaHHxhk7uDUIjkjL+FwzrHbuTN7HjA2zjyTBtTCZizBwPMMpxaDGzwGh3PYbuduuJHA2Mzbdrh+wwEGM6BzD+PWcv4MUMu/c7n7oVqAtrB/w6/lQI7B4dy2A7kbJOBaePDbIjkDpKUvOXfGmYeNM2e2pTFIHuYplkjA4xd+/jPGn3O+2eX2tycf+PCxzYaB73j7xg8fe3CHGBKARQozECf2HCBGCwr4QbqWUTAKRsEoGLYAAD8JW4ez2jWzAAAAAElFTkSuQmCC","orcid":"","institution":"Department of Gastroenterological Surgery, Toho University Omori Medical Center","correspondingAuthor":true,"prefix":"","firstName":"Yoko","middleName":"","lastName":"Oshima","suffix":""},{"id":359801328,"identity":"112799c3-93fc-43e5-a507-c513eadb92d4","order_by":2,"name":"fumiaki Shiratori","email":"","orcid":"","institution":"Department of Gastroenterological Surgery, Toho University Omori Medical Center","correspondingAuthor":false,"prefix":"","firstName":"fumiaki","middleName":"","lastName":"Shiratori","suffix":""},{"id":359801329,"identity":"ce3c1eb9-5b1e-43c1-a041-f08bfa43fedc","order_by":3,"name":"Takashi Suzuki","email":"","orcid":"","institution":"Department of Gastroenterological Surgery, Toho University Omori Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Takashi","middleName":"","lastName":"Suzuki","suffix":""},{"id":359801330,"identity":"809f6bc6-92da-4fa2-9cbc-40c7a0cac1f9","order_by":4,"name":"Satoshi Yajima","email":"","orcid":"","institution":"Department of Gastroenterological Surgery, Toho University Omori Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Satoshi","middleName":"","lastName":"Yajima","suffix":""},{"id":359801331,"identity":"882a924f-3075-44a6-b919-a29c1b34fca1","order_by":5,"name":"Kimihiko Funahashi","email":"","orcid":"","institution":"Department of Gastroenterological Surgery, Toho University Omori Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Kimihiko","middleName":"","lastName":"Funahashi","suffix":""},{"id":359801332,"identity":"a23d69f6-b545-44f4-b910-bda43356c4c2","order_by":6,"name":"Hideaki Shimada","email":"","orcid":"","institution":"Department of Gastroenterological Surgery, Toho University Omori Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Hideaki","middleName":"","lastName":"Shimada","suffix":""}],"badges":[],"createdAt":"2024-09-01 06:37:31","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5011542/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5011542/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s12029-025-01171-6","type":"published","date":"2025-01-27T15:57:05+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":66946290,"identity":"7d6175d2-f420-4841-b5ae-6d1a93d69725","added_by":"auto","created_at":"2024-10-18 09:43:38","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":273811,"visible":true,"origin":"","legend":"\u003cp\u003eA flowchart of patient selection for this study\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-5011542/v1/01bcfd685139e16218b510e0.png"},{"id":66946289,"identity":"60a3a1e4-05df-41c1-9fd3-68dc5f4caf48","added_by":"auto","created_at":"2024-10-18 09:43:38","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":192649,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003e(a)\u003c/strong\u003e Evaluation of basophil count as a predictive factor using receiver operating characteristic (ROC) curve in 1192 patients with gastric cancer. (\u003cstrong\u003eb) \u003c/strong\u003eDistribution of the number of gastric cancer patients by basophil\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-5011542/v1/4df239fe651d89ce42286689.png"},{"id":66944289,"identity":"db1c661b-7735-4cf9-9735-df40322f00db","added_by":"auto","created_at":"2024-10-18 09:35:38","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":98859,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of overall survival between high and low basophil groups\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-5011542/v1/1ea8b830a4bfe0165f4e1ad4.png"},{"id":66946291,"identity":"4d688cf7-1181-44cc-a970-6c3f8d5157eb","added_by":"auto","created_at":"2024-10-18 09:43:38","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":359971,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of overall survival between high and low basophil groups at each tumor stage. (\u003cstrong\u003ea)\u003c/strong\u003e stage Ⅰ, (\u003cstrong\u003eb)\u003c/strong\u003e stage Ⅱ, (\u003cstrong\u003ec)\u003c/strong\u003estage Ⅲ, (\u003cstrong\u003ed)\u003c/strong\u003e stage Ⅳ.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-5011542/v1/864db2636845ad3284e002a1.png"},{"id":75351168,"identity":"87eed527-6def-4773-81e7-dba6a2f3300f","added_by":"auto","created_at":"2025-02-03 16:07:07","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1275526,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5011542/v1/07391b26-05f0-453e-85d8-a3cc19ede6c5.pdf"},{"id":66944292,"identity":"4f7ddfb8-5e5b-43e5-9e1a-f4ff0d01f1ff","added_by":"auto","created_at":"2024-10-18 09:35:38","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":317454,"visible":true,"origin":"","legend":"","description":"","filename":"Tables.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5011542/v1/527098c0b5da1c9df6a644e7.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Association of preoperative low circulating basophil counts with the prognostic factor in gastric cancer","fulltext":[{"header":"Introduction","content":"\u003cp\u003eGastric cancer is the fourth and third leading cause of death globally and in Japan, accounting for approximately 800,000 and 40,000 deaths annually, respectively [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSeveral studies reported the association between neutrophils, lymphocytes, and C-reactive protein (CRP) in gastric cancer [\u003cspan additionalcitationids=\"CR4\" citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. A high neutrophil-to-lymphocyte ratio [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e], high CRP level [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e], and low lymphocyte count are considered poor prognostic factors [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e], and an association between these factors and tumor growth and progression has been indicated. However, the fraction of basophils is very small; thus, only one study [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] reported on the clinicopathological significance of basophils in patients with gastric cancer. Basophil is a type of granulocyte and accounts for \u0026lt;\u0026thinsp;1% of white blood cells in peripheral blood. Basophil is involved in allergic diseases and parasitic infections by regulating immunoglobulin E -mediated reactions and type 2 immune responses through various mediators, including histamine, leukotriene C4, and interleukin-4 and \u0026minus;\u0026thinsp;13 [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eClinicopathological significance of circulating basophils in esophageal cancer [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], gastric cancer [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e], and colorectal cancer [\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] have been reported in gastrointestinal cancer. These previous studies revealed that low circulating basophil count was associated with poor prognosis other than gastric cancer. These reports analyzed mixed populations, including both surgical and non-surgical cases, and only one report focused on surgical cases [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Wu C et al. discussed that the high basophil count around the tumor cells was associated with poor prognosis in advanced and/or recurrent gastric cancer [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Such tendency was not similar in esophageal cancer [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] and colorectal cancer [\u003cspan additionalcitationids=\"CR13\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. No studies analyzed the association between circulating basophil count and prognosis only focused on surgically treated gastric cancer.\u003c/p\u003e \u003cp\u003eTherefore, this study analyzed the clinicopathological and prognostic significance of preoperative circulating basophil count in patients with surgically treated gastric cancer to establish the cut-off value of basophil count as a derivation cohort.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy population\u003c/h2\u003e \u003cp\u003eA total of 1514 patients with primary gastric cancer underwent surgery at Toho University Omori Medical Center from January 2001 to December 2020. This retrospective study enrolled 1192 consecutive patients (811 males and 381 females with a median age of 68 years; range, 32\u0026ndash;96 years) after excluding patients who received preoperative chemotherapy, those who had residual gastric cancer, and double cancer (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The cut-off value was determined to classify circulating basophil count as low group and high group based on receiving operating characteristic curves, and then clinicopathological factors and overall prognosis were compared between these two groups. All patients were followed up until the end of December 2020 or death. The median follow-up period was 48 (range: 0\u0026ndash;60) months. The Ethics Committee of Toho University Omori Medical Center (#M23174 21320 21039 20200 20196 19056 18002) approved this study, conducted under the Declaration of Helsinki. Informed consent was obtained in the form of opt-out on the web-site. Those who rejected were excluded.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eCirculating basophil count and pathological factors\u003c/h2\u003e \u003cp\u003eWe analyzed circulating basophil count through routine blood tests within 7 days preoperatively. The tumor, node, and metastasis stage [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] were determined by pathological diagnosis using resected specimens. Correlation between basophil count and clinicopathological factors, such as age, gender, tumor depth, lymph node metastasis, distant metastasis, liver metastasis, CRP, lymphocyte count, and neutrophil count, were evaluated. Tumor depth was classified into the T1T2 (M, SM) and T3T4 (MP, SS, SE, SI) groups. Lymph node, distant, and liver metastases were classified as negative or positive.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eThe cut-off value of basophil count was set at 26/\u0026micro;l based on receiving operating characteristic curves for overall survival (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea). Univariate and multivariate analyses were performed to evaluate the clinicopathological and prognostic significance of low basophil count. The \u003cem\u003ep\u003c/em\u003e-value was calculated using Fisher\u0026rsquo;s exact test for univariate analysis. Overall survival probabilities were calculated using the product limit method of Kaplan\u0026ndash;Meier, considering overall deaths and the log-rank test was utilized to analyze the survival differences between the groups. The multivariate analysis calculated the odds ratio, 95% confidence interval, and \u003cem\u003ep\u003c/em\u003e-value using a logistic regression analysis. EZR was used for all statistical analyses [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Two-sided \u003cem\u003ep\u003c/em\u003e-values of \u0026lt;\u0026thinsp;0.05 indicated statistical significance.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eThe median basophil count of 1192 patients was 27/\u0026micro;l (0\u0026ndash;368/\u0026micro;l). We fixed the cut-off value of the basophil count as 26/\u0026micro;l based on the receiving operating characteristic analysis(Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003ea). We classified 586 (49.2%) patients into the high basophil group and 606 (50.8%) patients into the low basophil group using the cut-off value (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eb).\u003c/p\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eClinicopathological significance of low basophil count\u003c/h2\u003e \u003cp\u003eUnivariate analysis identified elderly age (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), high CRP (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), low lymphocyte count (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002), and low neutrophil count (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.002) to be significantly associated with low basophil count (Table\u0026nbsp;1). Multivariate analysis determined elderly age (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.009), high CRP (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and low neutrophil count (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) to be significantly associated with low basophil count (Table\u0026nbsp;2).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003ePrognostic significance of low basophil count on overall survival\u003c/h2\u003e \u003cp\u003eUnivariate analysis of all patients revealed a significantly worse prognosis of the low basophil group than that of the high basophil group (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.005, Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). The prognosis of both groups was almost similar, comparing the prognosis of both groups according to the stage, in stage I. However, the low basophil group demonstrated a worse prognosis than the high basophil group in stage II/III/IV (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eUnivariate and multivariate analyses of the prognostic effect of low basophil count on overall survival\u003c/h2\u003e \u003cp\u003eUnivariate analysis revealed that elderly age (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), T3T4 invasion depth (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), lymph node metastasis (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), distant metastasis (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), liver metastasis (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), high CRP (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), low lymphocytes (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), low neutrophils (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and low basophil count (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.005) were significantly associated with poor overall survival. Multivariate analysis determined elderly age (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001), T3T4 invasion depth (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), lymph node metastasis (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), high CRP (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), low lymphocyte count (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.039), high neutrophil count (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.028), and low basophil count (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.042) as independent risk factors for poor overall survival (Table\u0026nbsp;3).\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eNo study indicated the cut-off value of circulating basophil count in gastric cancer; thus, this study aimed to establish an appropriate cut-off value (\u0026lt;\u0026thinsp;26/\u0026micro;l) as the derivation cohort. We assessed the clinicopathological significance of preoperative circulating basophil count in surgically treated gastric cancer. Additionally, we revealed that low basophil count was associated with tumor progression. The low basophil count was an independent risk factor for poor overall survival. This study is the first to reveal an association between preoperative circulating basophil count and prognosis in surgically treated gastric cancer.\u003c/p\u003e \u003cp\u003eOther similar studies, indicated cut-off values for circulating basophil count at 25/\u0026micro;l (area under the curve\u0026thinsp;=\u0026thinsp;0.669) in colorectal cancer [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] and 20/\u0026micro;l (area under the curve\u0026thinsp;=\u0026thinsp;0.7208) in unresectable gastric cancer [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] based on receiver operating characteristic curves. This value was similar to the cut-off value set in our present study, so the cut-off value might be reasonable.\u003c/p\u003e \u003cp\u003ePeripheral blood cell count studies revealed low lymphocyte count [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] and high neutrophil count [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] as risk factors for poor prognosis in gastric cancer. Since basophils are negatively correlated with neutrophils, it is natural that low basophil counts are a poor prognostic factor. Our study revealed that low lymphocyte count, high neutrophil count, and low basophil count were independent poor prognostic factors. A significant correlation between low basophil, low lymphocyte, and neutrophil count was observed, which may reflect decreased hematopoietic function mainly due to aging. A significant correlation between low basophil count and high CRP level was observed because differentiation into neutrophils is prioritized during infiltration that causes high CRP levels, such as inflammation or infection.\u003c/p\u003e \u003cp\u003eThe immunohistochemical analysis of previous reports revealed that a large number of basophils infiltrating the tumor was a poor prognostic factor in gastric cancer [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Furthermore, it has been reported that there is a positive correlation between the infiltration of basophils into the tumor and the infiltration of M2 macrophages into the tumor in gastric cancer. Macrophages are known to promote tumor angiogenesis and distant metastasis [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], suggesting that basophils may also be immunologically involved in the tumor microenvironment in gastric cancer. There are only limited reports on the relationship between the number of basophils in peripheral blood and the number of basophils infiltrating into the tumor, and it is not yet fully understood. Chronic urticaria is a typical disease in which the number of basophils in the peripheral blood decreases. In patients with chronic urticaria, the number of basophils in the peripheral blood decreases as basophils are recruited to the skin, which is the main site of inflammation. [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] Considering the biological response of patients with chronic urticaria, gastric cancer patients may also similarly decrease the number of circulating basophils due to an increase in the number of basophils infiltrating the tumor. Regarding the prognosis in unresectable gastric cancer who were treated with immunotherapy, the high basophil group demonstrated a worse prognosis than the low basophil group [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. This contradicts our study results probably because the research participants were limited to recurrence and distant metastasis cases [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. The prognosis of the high and low basophil count groups was very similar in stage I. This indicates that the low basophil counts did not have any effects on the other cause of death in stage I. The absence of a statistically significant difference in stage III/IV was due to the insufficient number of cases.\u003c/p\u003e \u003cp\u003eThis study has some limitations. First, this is a retrospective single-center study. Second, this study did not investigate the patient\u0026rsquo;s history of immune diseases, vulnerabilities including bone marrow function, allergies, or use of immune-related drugs, including anti-allergy drugs and/or steroids. Third, this study included long periods of patients; thus, various adjuvant chemotherapy and systematic therapy after recurrence influenced the prognosis. The present study was a derivation cohort to fix the appropriate cut-off value of circulating basophil count. Further evaluation cohort is warranted to ensure the impact of circulating basophil count. Therefore, further multi-institutional studies are required to assess the effect of low circulating basophil counts on the survivals in patients with gastric cancer postoperatively.\u003c/p\u003e \u003cp\u003eIn conclusion, low basophil count was significantly associated with high neutrophil count and high CRP level, but low basophil count was an independent poor prognostic factor in patients with gastric cancer. Thus, preoperative circulating basophil count assessment may be useful for predicting the postoperative survival of patients with gastric cancer.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank MARUZEN-YUSHODO Co., Ltd. (https://kw.maruzen.co.jp/kousei-honyaku/) for the English language editing. We thank Seiko Otsuka for preparing the ethical documents.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;The authors have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMakiko Kawano, Hideaki Shimada, and Kimihiko Funahashi conceived and designed the current study. Makiko Kawano, Yoko Oshima, Fumiaki Shiratori, Takashi Suzuki, and Satoshi Yajima contributed to the acquisition of the patient\u0026rsquo;s clinicopathological data. Makiko Kawano and Yoko Oshima analyzed the patient data. Makiko Kawano and Hideaki Shimada drafted the manuscript. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical approval\u003c/strong\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Faculty of Medicine, Toho University Omori Medical Center (Tokyo, Japan; #M23174 21320 21039 20200 20196 19056 18002).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe participants were given the opportunity to decline to be enrolled in the study (opt-out).\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eSung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A et al (2021)Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 71:209-249. https://doi.org/10.3322/caac.21660\u003c/li\u003e\n\u003cli\u003eCancer Statistics. Cancer Information Service, National Cancer Center, Japan (Vital Statistics of Japan, Ministry of Health, Labour and Welfare). https://ganjoho.jp/reg_stat/statistics/data/dl/index.html\u003c/li\u003e\n\u003cli\u003eKong F, Gao F, Chen J, Zheng R, Liu H, Li X, Yang P et al (2016) Elevated serum C-reactive protein level predicts a poor prognosis for recurrent gastric cancer. Oncotarget. 7:55765-55770. https://doi.org/10.18632/oncotarget.9910 \u003c/li\u003e\n\u003cli\u003eFeng F, Zheng G, Wang Q, Liu S, Liu Z, Xu G, Fei Wang et al (2018) Low lymphocyte count and high monocyte count predicts poor prognosis of gastric cancer. BMC Gastroenterol. 18:148. https://doi.org/10.1186/s12876-018-0877-9\u003c/li\u003e\n\u003cli\u003eFukushima N, Masuda T, Tsuboi K, Takahashi K, Yuda M, Fujisaki M, Ikegami T et al (2024) Prognostic significance of the preoperative C-reactive protein-albumin-lymphocyte (CALLY) index on outcomes after gastrectomy for gastric cancer. Surgery Today. https://doi.org/10.1007/s00595-024-02813-1\u003c/li\u003e\n\u003cli\u003eShimada H, Takiguchi N, Kainuma O, Soda H, Ikeda A, Cho A, Miyazaki A et al (2010) High preoperative neutrophil-lymphocyte ratio predicts poor survival in patients with gastric cancer. Gastric Cancer. 13:170\u0026ndash;176. https://doi.org/10.1007/s10120-010-0554-3\u003c/li\u003e\n\u003cli\u003eYamamoto S, Kanzaki H, Sakaguchi C, Mouri H, Tsuzuki T, Nasu J, Kobayashi S et al (2023) Current prognostic factors of advanced gastric cancer patients treated with chemotherapy: real world data from a Japanese 12 institutions. Jpn J Clin Oncol. 53:928-935. https://doi.org/10.1093/jjco/hyad091\u003c/li\u003e\n\u003cli\u003eSuzuki T, Shimada H, Nanami T, Oshima Y, Yajima S, Ito M, Washizawa N et al (2016) Hyperfibrinogenemia is associated with inflammatory mediators and poor prognosis in patients with gastric cancer. Surg Today. 46:1394-1401. https://doi.org/10.1007/s00595-016-1339-z\u003c/li\u003e\n\u003cli\u003eWu C, Qiu Y, Zhang R, Li X, Liang H, Wang M, Li F et al (2022) Association of peripheral basophils with tumor M2 macrophage infiltration and outcomes of the anti-PD-1 inhibitor plus chemotherapy combination in advanced gastric cancer. J Transl Med. 4;20:386. https://doi.org/10.1186/s12967-022-03598-y\u003c/li\u003e\n\u003cli\u003ePoto R, Gambardella AR, Marone G, Schroeder JT, Mattei F, Schiavoni G, Varricchi G (2022) Basophils from allergy to cancer. Front Immunol. 13:1056838. https://doi.org/10.3389/fimmu.2022.1056838\u003c/li\u003e\n\u003cli\u003eMaruyama S, Okamura A, Kanie Y, Kuriyama K, Sakamoto K, Kanamori J, Imamura Y et al (2023) Prognostic significance of circulating basophil counts in patients who underwent esophagectomy for esophageal cancer. Langenbecks Arch Surg. 408:235. https://doi.org/10.1007/s00423-023-02977-3 \u003c/li\u003e\n\u003cli\u003eWei Y, Zhang X, Wang G, Zhou Y, Luo M, Wang S, Hong C (2018) The impacts of pretreatment circulating eosinophils and basophils on prognosis of stage Ⅰ-Ⅲ colorectal cancer. Asia Pac J Clin Oncol. 14:e243-e251. https://doi.org/10.1111/ajco.12871\u003c/li\u003e\n\u003cli\u003eLiu Q, Luo D, Cai S, Li Q, Li X (2020) Circulating basophil count as a prognostic marker of tumor aggressiveness and survival outcomes in colorectal cancer. Clin Transl Med. https://doi.org/10.1186/s40169-019-0255-4\u003c/li\u003e\n\u003cli\u003eGao L, Yuan C, Fu J, Tian T, Huang H, Zhang L, Li G et al (2023) Prognostic scoring system based on eosinophil- and basophil-related markers for predicting the prognosis of patients with stage II and stage III colorectal cancer: a retrospective cohort study. Front Oncol. 13:1182944. https://doi.org/10.3389/fonc.2023.1182944\u003c/li\u003e\n\u003cli\u003eJapanese Gastric Cancer Association. Japanese Classification of Gastric Carcinoma. 15th\u003csup\u003e \u003c/sup\u003eed. 2017;Tokyo:Kanehara Shuppan (in Japanese)\u003c/li\u003e\n\u003cli\u003eKanda Y (2012) Investigation of the freely available easy-to-use software \u0026lsquo;EZR\u0026rsquo; for medical statistics. Bone Marrow Transplant. 48:452-458. https://doi.org/10.1038/bmt.2012.244\u003c/li\u003e\n\u003cli\u003eChen Z, Chen W, Wang J, Zhu M, Zhuang Z (2015) Pretreated baseline neutrophil count and chemotherapy-induced neutropenia may be conveniently available as prognostic biomarkers in advanced gastric cancer. Intern Med J. 45:854-859. https://doi.org/10.1111/imj.12786\u003c/li\u003e\n\u003cli\u003eHe X, Cao Y, Gu Y, Fang H, Wang J, Liu X, Lv K et al (2021) Clinical Outcomes and Immune Metrics in Intratumoral Basophil-Enriched Gastric Cancer Patients. Ann Surg Oncol. 28:6439-6450. https://doi.org/10.1245/s10434-021-09815-0 \u003c/li\u003e\n\u003cli\u003eLewis CE, Harney AS, Pollard JW (2016) The Multifaceted Role of Perivascular Macrophages in Tumors. Cancer Cell. 30(1):18-25. https://doi.org/10.1016/j.ccell.2016.05.017\u003c/li\u003e\n\u003cli\u003eZheng Z, Jia S, Shao C, Shi Y (2020) Irradiation induces cancer lung metastasis through activation of the cGAS-STING-CCL5 pathway in mesenchymal stromal cells. Cell Death Dis. 7;11(5):326. https://doi.org/10.1038%2Fs41419-020-2546-5 \u003c/li\u003e\n\u003cli\u003eSaini S.S. (2023) Urticaria and basophils. Allergol Int. 72:369-374. https://doi.org/10.1016/j.alit.2023.05.001\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTables are available in the Supplementary Files section.\u003c/p\u003e\n"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-gastrointestinal-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijgc","sideBox":"Learn more about [Journal of Gastrointestinal Cancer](https://www.springer.com/journal/12029)","snPcode":"12029","submissionUrl":"https://submission.nature.com/new-submission/12029/3","title":"Journal of Gastrointestinal Cancer","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Gastric cancer, Basophil count, Prognosis","lastPublishedDoi":"10.21203/rs.3.rs-5011542/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5011542/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eBasophils play a crucial role in immunoglobulin E-mediated allergic reactions and parasitic infections. Recently, a low basophil count was reported to be a poor prognostic indicator in patients with malignant tumors. This study aimed to investigate the cut-off value to evaluate the clinicopathological and prognostic significance of the basophil count in patients with gastric cancer.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis study enrolled 1192 consecutive gastric cancer surgically treated between 2001 and 2020. The cut-off values were fixed at 26/\u0026micro;l based on the receiver of characteristics curves for overall survival, and 606 patients were classified as the low basophil group. The clinicopathological and prognostic significance of the low basophil count was assessed by univariate and multivariate analyses\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eElderly age (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.009), high C-reactive protein level (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), and low neutrophil count (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), are independently associated with low basophil count. The low basophil group demonstrated a significantly worse overall survival than the high basophil group (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.005). Although there was no significant difference in stage I, the low basophil group demonstrated poor overall survival in stage II/III/IV. The low basophil count was an independent risk factor for poor overall survival (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.042).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eLow basophil count was significantly associated with elderly age, high C-reactive protein level, and low neutrophil count (\u0026lt;\u0026thinsp;26/\u0026micro;l). And, low basophil count was an independent poor prognostic factor in patients with gastric cancer. Thus, preoperative circulating basophil count assessment may be useful for predicting the postoperative survival of patients with gastric cancer.\u003c/p\u003e","manuscriptTitle":"Association of preoperative low circulating basophil counts with the prognostic factor in gastric cancer","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-18 09:35:33","doi":"10.21203/rs.3.rs-5011542/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-09-27T13:18:15+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-09-25T07:10:41+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-09-10T02:15:46+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"120600608863174037749618346663972103927","date":"2024-09-09T08:21:21+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"146416774901545632970455757875694238281","date":"2024-09-03T21:00:29+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-09-02T00:29:42+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-09-02T00:23:48+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-09-01T23:19:00+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of Gastrointestinal Cancer","date":"2024-09-01T06:36:03+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-gastrointestinal-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"ijgc","sideBox":"Learn more about [Journal of Gastrointestinal Cancer](https://www.springer.com/journal/12029)","snPcode":"12029","submissionUrl":"https://submission.nature.com/new-submission/12029/3","title":"Journal of Gastrointestinal Cancer","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"0a5a2bf1-8ad3-4877-92fc-6ba523463819","owner":[],"postedDate":"October 18th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-02-03T15:59:40+00:00","versionOfRecord":{"articleIdentity":"rs-5011542","link":"https://doi.org/10.1007/s12029-025-01171-6","journal":{"identity":"journal-of-gastrointestinal-cancer","isVorOnly":false,"title":"Journal of Gastrointestinal Cancer"},"publishedOn":"2025-01-27 15:57:05","publishedOnDateReadable":"January 27th, 2025"},"versionCreatedAt":"2024-10-18 09:35:33","video":"","vorDoi":"10.1007/s12029-025-01171-6","vorDoiUrl":"https://doi.org/10.1007/s12029-025-01171-6","workflowStages":[]},"version":"v1","identity":"rs-5011542","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5011542","identity":"rs-5011542","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}