Pentraxin 3 as a promising biomarker for cancer detection: a systematic review and meta-analysis

Pentraxin 3 as a promising biomarker for cancer detection: a systematic review and meta-analysis | 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 Pentraxin 3 as a promising biomarker for cancer detection: a systematic review and meta-analysis Qindong Liang, Guangjie Zhang, Huaan Huang, Nai Xing, Shangchun Sheng, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.2.16075/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 Background Mounting studies reported that circulating pentraxin 3 (PTX3) expression level was significantly different between cancer patients and healthy groups, suggesting that PTX3 may be a potential biomarker for cancer detection. However, the results were inconsistent. In this paper, a systematic review and meta-analysis was performed to quantitatively assess the diagnostic value of PTX3 in cancer detection.Methods A comprehensive computerized literature search was conducted in Embase, PubMed, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure (CNKI) from inception to July 31, 2019. Eligible studies were identified and raw data were extracted. Diagnostic estimates were synthesized using STATA (version 12.0) and MetaDisc (version 1.4) statistical software.Results Overall, 9 studies from 8 citations with a total of 1408 cancer patiens and 3116 controls were included in this meta-analysis. The global sensitivity was 0.70 (95% confidence interval (CI): 0.67 – 0.72), and the specificity was 0.77 (95% CI: 0.75 – 0.78). The pooled positive likelihood ratio (PLR), negative likelihood ratio (NLR), and the diagnostic odds ratio (DOR) were 2.86 (95% CI: 2.29 – 3.56), 0.40 (95% CI: 0.32 – 0.50) and 7.38 (95% CI: 5.05 – 10.78), respectively. The merged AUC was 0.80 (95% CI: 0.76 – 0.83).Conclusion The serum PTX3 appears to be a reliable biomarker for cancer detection though large-scale multicenter studies are needed. Cancer Biology Oncology pentraxin 3 cancer diagnosis meta-analysis Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Background Cancer is a significant public health problem. Over the past several decades, cancer is becoming one of the leading causes of death ranked only second to angiocardiopathy worldwide though cancer management has advanced greatly. It is estimated, according to the World Health Organization, that the deaths from cancers will mount up to approximately 13.2 million in 2030[ 1 ]. In general, an early diagnosis and timely treatment are crucial in improving the overall survival rate among people suffering from cancer. The earlier the cancer is diagnosed, the easier the cancer is to treat and control. Whereas, most of the cancer patients are diagnosed at an advanced stage due to its aggression, early metastasis and the lack of characteristic early clinical features which may be useful in the early detection of the disease[ 2-4 ]. Meanwhile, the current reference gold standards for cancer diagnosis are mainly consist of biopsy, spiral computer tomography and magnetic resonance imaging. Though the biopsy show a good diagnostic performance in cancer screening, the invasiveness and uncomfortable experience for patients confine the broad application in clinic. Likewise, despite the good diagnostic accuracy in cancer detection, imaging techniques, like spiral computer tomography and magnetic resonance imaging, uaually get patients under the risk of exposure to radiation and are associated with relatively high costs[ 5-7 ]. Therefore, it is urgent to develop new methods with high diagnostic accuracy and low invasiveness for the early detection of cancer. Pentraxin 3 (PTX3), which is a member of the pentraxin superfamily, plays an important role in immune regulation, inflammation, cellular proliferation, and vascular remodeling[ 8-10 ]. PTX3 can be produced by several human cell types, for example, neutrophils, macrophages, fibroblasts, dentritic cells, smooth muscle cells, and endothelial cells[ 11 ]. Recently, a new wave of researches demonstrated that PTX3 might be a promising serological biomarker for various human malignancies, such as lung cancer, colorectal cancer, hepatocellular carcinoma, prostate cancer and pancreatic cancer[ 12-19 ]. Nevertheless, it is difficult to interpret the data because the results were inconsistent. To summarize the currently available data, a systematic review and meta-analysis was conducted to evaluate the diagnostic performance of PTX3 in cancer screening based on several clinical trials. Methods This study was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-analysis (PRISMA) statement[ 20 , 21 ] . Publication search strategy A comprehensive literature search was carried out in PubMed, Embase, Cochrane Library, Web of Science, and China National Knowledge Infrastructure (CNKI) from inception up to July 31, 2019. The search words used for article identification included: i) “cancer” or “carcinoma” or “tumor” or “neoplasma”; ii) “pentraxin 3” or “PTX3”; iii) “diagnostic” or “diagnosis”. Meanwhile, the literatures cited by all the suitable studies were scanned to acquire more relevant citations. Additionally, no language restrictions were applied in this systematic review and meta-analysis. Study selection Two researchers (Qindong Liang and Guangjie Zhang) carefully scanned all the searched papers and independently identified the articles suitable for the systematic review. The articles were considered eligible if they satisfied all the following criteria: 1) patients with cancer were confirmed by histopathological examination or endoscopy; 2) blood samples were collected before any operation; 3) level of pentraxin 3 was measured in serum, plasma or blood; 4) the study was a case-control, prospective or retrospective cohort design; 5) sufficient data to draw 2 by 2 contingency tables. On the contrary, letters, commentary, abstracts presented in conferences, case reports and reviews were excluded. For duplicate publications adopting the same population, we selected the most recent article or the one with most informative data. Quality assessment Study quality assessment was completed independently by the same two researchers according to the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) checklist[ 22 ]. Any disagreement was settled through thorough discussion, and when it was necessary, arbitration by a third researcher to reach an agreement. Data extraction Two investigators (Qindong Liang and Guangjie Zhang) meticulously scrutinized all the included articles and the relevant data of each enrolled studies was extracted. For each research, the following data were collected: 1) study characteristics (the first author’s name, year of publication, country, assay method, the number of cases and control groups); 2) the diagnostic data (such as sensitivity, specificity, cutoff value, etc.). The exact number of 2 by 2 contingency tables (true positive (TP), false positive (FP), true negative (TN) and false negative (FN)) were obtained directly or by recalculation. Statistic analysis The global diagnostic variables with corresponding 95% confidence intervals (CIs), like sensitivity, specifcity, PLR, NLR, and DOR were calculated using STATA (version 12.0) and Meta-Disc (version 1.4) software[ 23 ]. The SROC curve was drawn to evaluate the diagnostic performance and to calculate the area under curve (AUC). The pooled AUC was used to describe the overall accuracy as a potential summary of the SROC curve. Meanwhile, Spearman correlation test was performed to quantify the threshold effect. Heterogeneity induced by non-threshold effect between the included studies was measured by the Cochran Q method and the inconsistency index (I 2 ) test. P value 50% indicated a significant heterogeneity existing in our systematic review. Moreover, meta-regression analysis was conducted to find out the sources of heterogeneity. At last, publication bias was determined by Deek’ regression test. P value < 0.05 was considered to be statistically significant. Results Study selection Running the systematic search, a total of 121 citations were found: 35 in PubMed, 61 in Embase, 0 in Cochrane Library, 11 in Web of Science, and 14 in CNKI, respectively. As depicted in the flowchart ( Figure 1 ), 20 duplicate records were removed. Furthermore, after scanning the titles and abstracts, 83 records were discarded because they were irrelevant studies, abstracts, books, letters, meetings, or comments. Subsequently, 18 studies were identified for full-text reading. After reading the full-text of the 18 studies, 10 studies were excluded for the following reasons: two were not about cancer[ 24 , 25 ], five did not refer to circulating PTX3[ 26-30 ], two articles did not report the diagnostic performance of circulating PTX3 in cancer detection[ 31 , 32 ], one paper did not present sufficient data[ 33 ]. Finally, eight papers involving nine studies were included in this meta-analysis[ 12-16 , 34-36 ]. Studies characteristics The main features of the nine included studies, such as name of the first author, year of publication, country, cancer type, number of patients and controls, sensitivity and specificity, are presented in Table 1 by descending order of publication year. The included studies enrolled a total of 1408 cancer patients and 3116 control individuals. Among these studies, six were conducted in China[ 12 , 15 , 34-36 ], two in Italy[ 13 , 14 ], and one in USA[ 16 ]. Besides, six researches investigated the diagnostic value of PTX3 for lung cancer, and one for gastric cancer, colorectal cancer and prostate cancer, each. The publication date of the included studies rang from 2011 to 2019. All these studies used the method of enzyme linked immunosorbent assay (ELISA) to detect the serum level of PTX3. Quality assessment To assess the quality of these nine eligible studies, a graph of risk of bias and applicability concerns was drawn. As shown in Figure 2 , only one study[ 13 ] conformed to all the quality assessment items, and the bias of the eligible studies was mainly focused on “patients selection” and “index test”. Specially, in the domain of patient selection, 5 studies[ 12 , 14-16 ] did not state whether the study avoided inappropriate exclusions. Meanwhile, in the domain of index test, 6 studies[ 14 , 15 , 34-36 ] did not adopt blinded method and one study[ 12 ] was unclear if blinded method was used. Generally, all the included nine studies could be considered to be of upper quality. Diagnostic accuracy analysis Significant heterogeneity in sensitivity (I 2 = 83%) and specificity (I 2 = 87.4%) was observed. Therefore, a random effects model was adopted in this meta-analysis to assess the diagnostic accuracy of PTX3 in cancer screening. Shown in Figure 3 , the global sensitivity (SE) was 0.70 (95% confidence interval (CI): 0.67 – 0.72) , and the specificity (SP) was 0.77 (95% CI: 0.75 – 0.78). The pooled positive likelihood ratio (PLR), negative likelihood ratio (NLR), and the diagnostic odds ratio (DOR) were 2.86 (95% CI: 2.29 – 3.56), 0.40 (95% CI: 0.32 – 0.50) and 7.38 (95% CI: 5.05 – 10.78), respectively ( Figure 4 and Figure 5 ). The area under the summary receiver operator characteristic (SROC) curve was 0.80 (95% CI: 0.76 – 0.83) ( Figure 6 ). Threshold effect analysis and Heterogeneity exploration Spearman’s rank correlation analysis was carried out to evaluate the heterogeneity caused by threshold effect between the included studies (run on MetaDisc, version 1.4). Spearman correlation coefficient was -0.233 and the P- value was 0.546 (p > 0.05), indicating that threshold effect was not the source of heterogeneity in this study. Nevertheless, heterogeneity indeed existed as the I 2 of SE and SP were 83% and 87.4%, separately. Thereupon, meta-regression analysis was conducted to explore the sources of heterogeneity (performed on MetaDisc, version 1.4). We considered etnnicity, assay kit, sample size, and cancer type as the most possible factors causing heterogeneity. However, no satisfactory clues were observed. The results of meta-regression analysis are listed in Table 2 . Publication bias Deeks’ funnel plot asymmetry analsysis (tested with STATA, version 12.0) was run to assess the potential bias between the nine eligible studies. As shown in Figure 7 , no indication of publication bias was observed (t = 0.46; p > 0.05). Discussion Though traditional surgical specimens or biopsy tissues and imaging techniques are used in the cancer diagnosis, limitations still exist mainly due to the invasive procedures and the delayed reflection of tumor dynamic changes. Besides, cancer patients are usually found at the relatively late stages and the outcome is generally poor. Therefore, it is urgent to develop new methods with high performance for cancer diagnosis using minimally invasive procedures. PTX3, also named TSG14, has been known as a candidate novel marker of inflammation[ 37 ], especially cancer-related inflammation[ 38 , 39 ]. PTX3 involves in many crucial biological events, including cellular proliferation, angiogenesis, apoptosis, cancer cell invasion and metastasis[ 8 , 40 ]. Recent studies suggested PTX3 could be a potential serum biomarker for cancer screening[ 12-16 ]. However, to the best of our knowledge, there is no systematic evidence-based evaluation for PTX3 as a tumor marker in cancer detection. In this study, we performed a systematic review and meta-analysis to assess the diagnostic performance of circulating PTX3 in cancer diagnosis. In this meta-analysis, a total of eight papers with 4524 individuals (1408 cancer patients and 3116 controls) were enrolled. Pooling the data from the included studies presented a combined SE of 0.70 (95% CI: 0.67 – 0.72) and a combined SP of 0.77 (95% CI: 0.75 – 0.78). Diagnostic odds ratio (DOR), a merged power of SE and SP, is a metric of overall diagnostic performance. A higher DOR, a better diagnostic accracy. The global DOR of PTX3 in this study is 7.38 (95% CI: 5.05 – 10.78), implying that PTX3 was of good diagnostic performance in cancer screening. To further investigate the diagnostic performance, we drew the SROC curve and calculated the corresponding AUC. Generally speaking, an AUC value of 0.75 to 0.92 means a good overall diagnostic performance, 0.92 to 0.96 means very good , and 0.97 to 1 means excellent[ 41 , 42 ]. The AUC of SROC curve for PTX3 was 0.8 (95% CI: 0.76 – 0.83), suggesting a good diagnostic accuracy. All of these results imply that PTX3 could be a novel promising diagnostic biomarker in cancer detection. Our study has several advantages. Firstly, the computerised search did not involve any language restriction on the publications in order to enroll more suitable studies besides english version. Secondly, our study is the first systematic review to verify the overall diagnostic accuracy of circulating PTX3 in cancer screening. Thirdly, PTX3 could be a potential biomarker for cancer with minimal invasiveness comparing to bioscopy and pathological examination. However, our study also has some weaknesses. At first, though meticulous comprehensive search was carried out in PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), only nine eligible studies were included in this meta-analysis. Besides, substantial heterogeneity in sensitivity (I 2 = 83%) and specificity (I 2 = 87.4%) exists between the included studies. According to the results of Spearman’s rank correlation analysis (Spearman coefficient = -0.233, p value = 0.546 ), threshold effect was not the source of heterogeneity. Furthermore, we conducted meta-regression analysis to identify the factor(s) causing heterogeneity. Several covariates, like etnnicity, assay kit, sample size, and cancer type were adopted as the most possible source(s) of heterogeneity. Unfortunately, no statistical significant evidence was obtained. What’s more, although there was no significant publication bias among the studies presented by Deeks’ funnel plot asymmetry analsysis ( Figure 7 ), some latent bias may still exists because positive results are likely to be reported. Conclusions In conclusion, this systematic review and meta-analysis provide convincing evidence that PTX3 is of considerable diagnostic accuracy and may be a potential biomarker in cancer detection. However, as the current diagnostic data are limited, more multicenter, well-designed high quality trials with large sample size should be done to strengthen the theory of PTX3 in cancer diagnosis. Abbreviations PTX3: pentraxin 3; GC: gastric cancer; CRC: colorectal cancer; LC: lung cancer; PC: prostate cancer; N: number; NR: not report; CNKI: Chinese National Knowledge Infrastructure; SE: sensitivity; SP: specificity; PLR: positive likelihood ratio; NLR: negative likelihood ratio; DOR: diagnostic odds ratio; SROC: summary receiver operator characteristic; AUC: area under curve; TP: true positive; FP: false positive; TN: true negative; FN: false negative; ELISA: enzyme linked immunosorbent assay; PRISMA: preferred reporting items for systematic reviews and meta-analysis; QUADAS-2: quality assessment of diagnostic accuracy studies 2. Declarations Acknowledgement NA Authors’ contributions Changguo Gu designed this systematic review and meta-analysis; Qindong Liang and Guangjie Zhang carried out the literature search and drafted the manuscript; Qindong Liang, Guangjie Zhang and Huaan Huang analyzed the data; Nai Xing, Shangchun Sheng and Changguo Gu were involved in revising the manuscript; all the authors read and approved the final manuscript. Funding This work was supported by the Youth Science Fund Project of National Nature Science Foundation of China ( NO. 81702101). Availability of data and materials Data and materials are available upon request. Ethics approval and consent to participate This study was approved by the Ethics committee of Affiliated Hospital & Clinical Medical College of Chengdu University. The patients enrolled Consent for publication Not applicable. Competing interests The authors declare that they have no competing interests. Author details 1 Department of Clinical Laboratory, Affiliated Hospital & Clinical Medical College of Chengdu University, No.82 North Second Section Second Ring Road, Jin-Niu District, Chengdu, Sichuan 610081 China; 2 Department of Clinical Laboratory, Chengdu Fifth People’s Hospital, No. 33 Mashi Street, Wenjiang District, Chengdu, Sichuan 611130, China References McGuire S: World Cancer Report 2014. Geneva, Switzerland: World Health Organization, International Agency for Research on Cancer, WHO Press, 2015 . Advances in Nutrition 2016, 7 (2):418-419. Gupta AK, Brenner DE, Turgeon DK: Early detection of colon cancer: new tests on the horizon . Molecular diagnosis & therapy 2008, 12 (2):77-85. Kelsen DP, Ginsberg R, Pajak TF, Sheahan DG, Gunderson L, Mortimer J, Estes N, Haller DG, Ajani J, Kocha W et al : Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer . The New England journal of medicine 1998, 339 (27):1979-1984. Portenoy RK, Thaler HT, Kornblith AB, Lepore JM, Friedlander-Klar H, Coyle N, Smart-Curley T, Kemeny N, Norton L, Hoskins W et al : Symptom prevalence, characteristics and distress in a cancer population . Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation 1994, 3 (3):183-189. Mahadevia PJ, Fleisher LA, Frick KD, Eng J, Goodman SN, Powe NR: Lung cancer screening with helical computed tomography in older adult smokers: a decision and cost-effectiveness analysis . Jama 2003, 289 (3):313-322. Ganti AK, Mulshine JL: Lung cancer screening . The oncologist 2006, 11 (5):481-487. Aberle DR, Adams AM, Berg CD, Black WC, Clapp JD, Fagerstrom RM, Gareen IF, Gatsonis C, Marcus PM, Sicks JD: Reduced lung-cancer mortality with low-dose computed tomographic screening . The New England journal of medicine 2011, 365 (5):395-409. Baruah P, Dumitriu IE, Peri G, Russo V, Mantovani A, Manfredi AA, Rovere-Querini P: The tissue pentraxin PTX3 limits C1q-mediated complement activation and phagocytosis of apoptotic cells by dendritic cells . Journal of leukocyte biology 2006, 80 (1):87-95. Mantovani A, Garlanda C, Bottazzi B: Pentraxin 3, a non-redundant soluble pattern recognition receptor involved in innate immunity . Vaccine 2003, 21 Suppl 2 :S43-47. Garlanda C, Bottazzi B, Bastone A, Mantovani A: Pentraxins at the crossroads between innate immunity, inflammation, matrix deposition, and female fertility . Annual review of immunology 2005, 23 :337-366. Lin Q, Fu F, Shen L, Zhu B: Pentraxin 3 in the assessment of ventilator-associated pneumonia: an early marker of severity . Heart & lung : the journal of critical care 2013, 42 (2):139-145. Liu B, Zhao Y, Guo L: Increased serum pentraxin-3 level predicts poor prognosis in patients with colorectal cancer after curative surgery, a cohort study . Medicine 2018, 97 (40):e11780. Infante M, Allavena P, Garlanda C, Nebuloni M, Morenghi E, Rahal D, Roncalli M, Cavuto S, Pesce S, Monari M et al : Prognostic and diagnostic potential of local and circulating levels of pentraxin 3 in lung cancer patients . International journal of cancer 2016, 138 (4):983-991. Stallone G, Cormio L, Netti GS, Infante B, Selvaggio O, Fino GD, Ranieri E, Bruno F, Prattichizzo C, Sanguedolce F et al : Pentraxin 3: a novel biomarker for predicting progression from prostatic inflammation to prostate cancer . Cancer research 2014, 74 (16):4230-4238. Zhang D, Ren WH, Gao Y, Wang NY, Wu WJ: Clinical significance and prognostic value of pentraxin-3 as serologic biomarker for lung cancer . Asian Pacific journal of cancer prevention : APJCP 2013, 14 (7):4215-4221. Diamandis EP, Goodglick L, Planque C, Thornquist MD: Pentraxin-3 is a novel biomarker of lung carcinoma . Clinical cancer research : an official journal of the American Association for Cancer Research 2011, 17 (8):2395-2399. Di Caro G, Carvello M, Pesce S, Erreni M, Marchesi F, Todoric J, Sacchi M, Montorsi M, Allavena P, Spinelli A: Circulating Inflammatory Mediators as Potential Prognostic Markers of Human Colorectal Cancer . PloS one 2016, 11 (2):e0148186. Song T, Wang C, Guo C, Liu Q, Zheng X: Pentraxin 3 overexpression accelerated tumor metastasis and indicated poor prognosis in hepatocellular carcinoma via driving epithelial-mesenchymal transition . Journal of Cancer 2018, 9 (15):2650-2658. Kondo S, Ueno H, Hosoi H, Hashimoto J, Morizane C, Koizumi F, Tamura K, Okusaka T: Clinical impact of pentraxin family expression on prognosis of pancreatic carcinoma . British journal of cancer 2013, 109 (3):739-746. Moher D, Liberati A, Tetzlaff J, Altman DG: Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement . Ann Intern Med 2009, 151 (4):264-269, W264. Page MJ, Moher D: Evaluations of the uptake and impact of the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) Statement and extensions: a scoping review . Syst Rev 2017, 6 (1):263. Whiting PF, Rutjes AW, Westwood ME, Mallett S, Deeks JJ, Reitsma JB, Leeflang MM, Sterne JA, Bossuyt PM: QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies . Ann Intern Med 2011, 155 (8):529-536. Zamora J, Abraira V, Muriel A, Khan K, Coomarasamy A: Meta-DiSc: a software for meta-analysis of test accuracy data . BMC Med Res Methodol 2006, 6 :31. Ozsu S, Abul Y, Mentese A, Bektas H, Uzun A, Ozlu T: Pentraxin-3: A novel biomarker for the differentiation of parapneumonic effusion and malignant pleural effusion . European Respiratory Journal 2012, 40 ((Ozsu S.; Abul Y.; Mentese A.; Bektas H.; Uzun A.; Ozlu T.)). Zhou X, Kang F, Wang S, Wang J: Diagnosis efficacy of plasma PTX3 under the guidance of 18F-FDG PET/CT in patients with Takayasu's arteritis . Journal of Nuclear Medicine 2017, 58 ((Kang F.) Xi'An, China). Liu C, Yao Y, Wang W: Pentraxin-3 as a prognostic marker in patients with small-cell lung cancer . Med Oncol 2014, 31 (10):014-0207. Locatelli M, Ferrero S, Martinelli Boneschi F, Boiocchi L, Zavanone M, Maria Gaini S, Bello L, Valentino S, Barbati E, Nebuloni M et al : The long pentraxin PTX3 as a correlate of cancer-related inflammation and prognosis of malignancy in gliomas . Journal of neuroimmunology 2013, 260 (1-2):99-106. Miyake M, Goodison S, Chang M, Dai Y, Urquidi V, Rosser CJ: A multi-analyte assay for the noninvasive detection of bladder cancer . Journal of Clinical Oncology 2013, 31 (6). Peng X, Xue H, Lü L, Shi P, Wang J: Accumulated promoter methylation as a potential biomarker for esophageal cancer . Oncotarget 2017, 8 (1):679-691. Urquidi V, Goodison S, Ross S, Chang M, Dai Y, Rosser CJ: Diagnostic potential of urinary α1-antitrypsin and apolipoprotein e in the detection of bladder cancer . Journal of Urology 2012, 188 (6):2377-2383. Takeda N, Asai K, Ijiri N, Yamamoto N, Watanabe T, Kamoi H, Kanazawa H, Hirata K: Pentraxin-3 as a Biomarker for Febrile Neutropenia in Patients with Lung Cancer . Osaka city medical journal 2015, 61 (1):43-52. Zhang J, Wang TY, Niu XC: Increased Plasma Levels of Pentraxin 3 Are Associated with Poor Prognosis of Colorectal Carcinoma Patients . The Tohoku journal of experimental medicine 2016, 240 (1):39-46. Goodison S, Chang M, Dai Y, Urquidi V, Rosser CJ: A Multi-Analyte Assay for the Non-Invasive Detection of Bladder Cancer . PloS one 2012, 7 (10). Chen L: Application value of serum Pentraxin-3 in diagnosis of gastric cancer . Laboratory Medicine and Clinic 2019(03):343-346. Lu K: The diagnostic value of the levels of CYFRA21-1, Pentraxin-3, ProGRP for non-small cell lung cancer . China Journal of Laboratory Diagnosis 2016(03):378-380. Xu JZ, H: The value of serum pentraxin-3 combined with HE4 in NSCLC diagnosis and prognosis Chinese Journal of Clinical Laboratory Science 2015, 33 (04):282-284. Ozsu S, Abul Y, Mentese A, Bektas H, Uzun A, Ozlu T, Porcel JM: Pentraxin-3: A novel biomarker for discriminating parapneumonic from other exudative effusions . Respirology 2013, 18 (4):657-662. Germano G, Frapolli R, Simone M, Tavecchio M, Erba E, Pesce S, Pasqualini F, Grosso F, Sanfilippo R, Casali PG et al : Antitumor and anti-inflammatory effects of trabectedin on human myxoid liposarcoma cells . Cancer research 2010, 70 (6):2235-2244. Lai CS, Li S, Chai CY, Lo CY, Dushenkov S, Ho CT, Pan MH, Wang YJ: Anti-inflammatory and antitumor promotional effects of a novel urinary metabolite, 3',4'-didemethylnobiletin, derived from nobiletin . Carcinogenesis 2008, 29 (12):2415-2424. Rutkowski MJ, Sughrue ME, Kane AJ, Mills SA, Parsa AT: Cancer and the complement cascade . Molecular cancer research : MCR 2010, 8 (11):1453-1465. Swets JA: Measuring the accuracy of diagnostic systems . Science 1988, 240 (4857):1285-1293. Jones CM, Athanasiou T: Summary receiver operating characteristic curve analysis techniques in the evaluation of diagnostic tests . The Annals of thoracic surgery 2005, 79 (1):16-20. Supplementary Files PRISMAChecklist2009.doc 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-6730","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research article","associatedPublications":[],"authors":[{"id":183850,"identity":"3e5b613b-d6e5-4789-9540-2a7dd19ba6ad","order_by":1,"name":"Qindong 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College of Chengdu University","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Shangchun","middleName":"","lastName":"Sheng","suffix":""},{"id":183855,"identity":"e0b70d93-1c39-4654-a45e-9122f04e705d","order_by":6,"name":"Changguo Gu","email":"","orcid":"","institution":"Chengdu Fifth people's Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Changguo","middleName":"","lastName":"Gu","suffix":""}],"badges":[],"createdAt":"2019-10-09 19:50:57","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.2.16075/v1","doiUrl":"https://doi.org/10.21203/rs.2.16075/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":128862,"identity":"806868a2-bf74-4fe3-9eb0-0ffddfd7d258","added_by":"auto","created_at":"2019-10-15 23:07:07","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":103410,"visible":true,"origin":"","legend":"Flowchart of eligible studies selection.","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/015da615-38d4-4c97-b429-a85d18371c2a/v1/1.png"},{"id":128864,"identity":"ab1289be-16ca-48af-80b4-82fb384bf1a7","added_by":"auto","created_at":"2019-10-15 23:07:07","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":169154,"visible":true,"origin":"","legend":"Quality assessment of the nine included studies.","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/015da615-38d4-4c97-b429-a85d18371c2a/v1/2.png"},{"id":128865,"identity":"da92ef15-1d1a-4025-a834-615631d3da0e","added_by":"auto","created_at":"2019-10-15 23:07:08","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":317295,"visible":true,"origin":"","legend":"Forest plots of sensitivity and specificity of PTX3 in cancer diagnosis.","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/015da615-38d4-4c97-b429-a85d18371c2a/v1/3.png"},{"id":128866,"identity":"a800fff4-da8a-4681-862c-0ae791cf9550","added_by":"auto","created_at":"2019-10-15 23:07:08","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":243786,"visible":true,"origin":"","legend":"Forest plots for Positive Likelihood Ratio and Negative Likelihood Ratio of PTX3 in cancer diagnosis.","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/015da615-38d4-4c97-b429-a85d18371c2a/v1/4.png"},{"id":128867,"identity":"42a0aec6-bc1b-4811-b0ac-885c0ffa411e","added_by":"auto","created_at":"2019-10-15 23:07:08","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":148138,"visible":true,"origin":"","legend":"Diagnostic Odds Ratio of PTX3 in cancer diagnosis.","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/015da615-38d4-4c97-b429-a85d18371c2a/v1/5.png"},{"id":128868,"identity":"af25050e-0cc0-4c29-8957-4af0e8fb406a","added_by":"auto","created_at":"2019-10-15 23:07:08","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":254242,"visible":true,"origin":"","legend":"Summary receiver operating characteristic curve.","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/015da615-38d4-4c97-b429-a85d18371c2a/v1/6.png"},{"id":128869,"identity":"e7641bb0-3d40-47c0-af78-860966deea6b","added_by":"auto","created_at":"2019-10-15 23:07:08","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":110704,"visible":true,"origin":"","legend":"Deeks’ funnel plot of publication bias.","description":"","filename":"7.png","url":"https://assets-eu.researchsquare.com/files/015da615-38d4-4c97-b429-a85d18371c2a/v1/7.png"},{"id":13477496,"identity":"d1fa8633-23ea-4513-a8c5-2e1525e5ef9d","added_by":"auto","created_at":"2021-09-16 21:31:27","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2211947,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6730/v1/9f342aa6-c424-4daf-a5d0-0779f71a0b07.pdf"},{"id":128861,"identity":"e7240f6b-cd9f-4649-be2a-ebac8da04784","added_by":"auto","created_at":"2019-10-15 23:07:07","extension":"doc","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":61440,"visible":true,"origin":"","legend":"","description":"","filename":"PRISMAChecklist2009.doc","url":"https://assets-eu.researchsquare.com/files/015da615-38d4-4c97-b429-a85d18371c2a/v1/PRISMA Checklist 2009.doc"}],"financialInterests":"","formattedTitle":"Pentraxin 3 as a promising biomarker for cancer detection: a systematic review and meta-analysis","fulltext":[{"header":"Background","content":"\u003cp\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp; Cancer is a significant public health problem. Over the past several decades, cancer is becoming one of the leading causes of death ranked only second to angiocardiopathy worldwide though cancer management has advanced greatly. It is estimated, according to the World Health Organization, that the deaths from cancers will mount up to approximately 13.2 million in 2030[\u003ca href=\"#_ENREF_1\"\u003e1\u003c/a\u003e]. In general, an early diagnosis and timely treatment are crucial in improving the overall survival rate among people suffering from cancer. The earlier the cancer is diagnosed, the easier the cancer is to treat and control. Whereas, most of the cancer patients are diagnosed at an advanced stage due to its aggression, early metastasis and the lack of characteristic early clinical features which may be useful in the early detection of the disease[\u003ca href=\"#_ENREF_2\"\u003e2-4\u003c/a\u003e]. Meanwhile, the current reference gold standards for cancer diagnosis are mainly consist of biopsy, spiral computer tomography and magnetic resonance imaging. Though the biopsy show a good diagnostic performance in cancer screening, the invasiveness and uncomfortable experience for patients confine the broad application in clinic. Likewise, despite the good diagnostic accuracy in cancer detection, imaging techniques, like spiral computer tomography and magnetic resonance imaging, uaually get patients under the risk of exposure to radiation and are associated with relatively high costs[\u003ca href=\"#_ENREF_5\"\u003e5-7\u003c/a\u003e]. Therefore, it is urgent to develop new methods with high diagnostic accuracy and low invasiveness for the early detection of cancer.\u003c/p\u003e\n\u003cp\u003ePentraxin 3 (PTX3), which is a member of the pentraxin superfamily, plays an important role in immune regulation, inflammation, cellular proliferation, and vascular remodeling[\u003ca href=\"#_ENREF_8\"\u003e8-10\u003c/a\u003e]. PTX3 can be produced by several human cell types, for example, neutrophils, macrophages, fibroblasts, dentritic cells, smooth muscle cells, and endothelial cells[\u003ca href=\"#_ENREF_11\"\u003e11\u003c/a\u003e]. Recently, a new wave of researches demonstrated that PTX3 might be a promising serological biomarker for various human malignancies, such as lung cancer, colorectal cancer, hepatocellular carcinoma, prostate cancer and pancreatic cancer[\u003ca href=\"#_ENREF_12\"\u003e12-19\u003c/a\u003e]. Nevertheless, it is difficult to interpret the data because the results were inconsistent.\u003c/p\u003e\n\u003cp\u003eTo summarize the currently available data, a systematic review and meta-analysis was conducted to evaluate the diagnostic performance of PTX3 in cancer screening based on several clinical trials.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis study was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-analysis (PRISMA) statement[\u003ca href=\"#_ENREF_20\"\u003e20\u003c/a\u003e, \u003ca href=\"#_ENREF_21\"\u003e21\u003c/a\u003e] .\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePublication search strategy\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u0026nbsp;\u0026nbsp; A comprehensive literature search was carried out in PubMed, Embase, Cochrane Library, Web of Science, and China National Knowledge Infrastructure (CNKI) from inception up to July 31, 2019. The search words used for article identification included: i) \u0026ldquo;cancer\u0026rdquo; or \u0026ldquo;carcinoma\u0026rdquo; or \u0026ldquo;tumor\u0026rdquo; or \u0026ldquo;neoplasma\u0026rdquo;; ii) \u0026ldquo;pentraxin 3\u0026rdquo; or \u0026ldquo;PTX3\u0026rdquo;; iii) \u0026ldquo;diagnostic\u0026rdquo; or \u0026ldquo;diagnosis\u0026rdquo;. Meanwhile, the literatures cited by all the suitable studies were scanned to acquire more relevant citations. Additionally, no language restrictions were applied in this systematic review and meta-analysis.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy selection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTwo researchers (Qindong Liang and Guangjie Zhang) carefully scanned all the searched papers and independently identified the articles suitable for the systematic review. The articles were considered eligible if they satisfied all the following criteria: 1) patients with cancer were confirmed by histopathological examination or endoscopy; 2) blood samples were collected before any operation; 3) level of pentraxin 3 was measured in serum, plasma or blood; 4) the study was a case-control, prospective or retrospective cohort design; 5) sufficient data to draw 2 by 2 contingency tables. On the contrary, letters, commentary, abstracts presented in conferences, case reports and reviews were excluded. For duplicate publications adopting the same population, we selected the most recent article or the one with most informative data.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eQuality assessment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eStudy quality assessment was completed independently by the same two researchers according to the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) checklist[\u003ca href=\"#_ENREF_22\"\u003e22\u003c/a\u003e]. Any disagreement was settled through thorough discussion, and when it was necessary, arbitration by a third researcher to reach an agreement.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData extraction\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTwo investigators (Qindong Liang and Guangjie Zhang) meticulously scrutinized all the included articles and the relevant data of each enrolled studies was extracted. For each research, the following data were collected: 1) study characteristics (the first author\u0026rsquo;s name, year of publication, country, assay method, the number of cases and control groups); 2) the diagnostic data (such as sensitivity, specificity, cutoff value, etc.). The exact number of 2 by 2 contingency tables (true positive (TP), false positive (FP), true negative (TN) and false negative (FN)) were obtained directly or by recalculation.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStatistic analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe global diagnostic variables with corresponding 95% confidence intervals (CIs), like sensitivity, specifcity, PLR, NLR, and DOR were calculated using STATA (version 12.0) and Meta-Disc (version 1.4) software[\u003ca href=\"#_ENREF_23\"\u003e23\u003c/a\u003e]. The SROC curve was drawn to evaluate the diagnostic performance and to calculate the area under curve (AUC). The pooled AUC was used to describe the overall accuracy as a potential summary of the SROC curve. Meanwhile, Spearman correlation test was performed to quantify the threshold effect. Heterogeneity induced by non-threshold effect between the included studies was measured by the Cochran Q method and the inconsistency index (I\u003csup\u003e2\u003c/sup\u003e) test. P value \u0026lt; 0.1 and I\u003csup\u003e2\u003c/sup\u003e value \u0026gt; 50% indicated a significant heterogeneity existing in our systematic review. Moreover,\u0026nbsp; meta-regression analysis was conducted to find out the sources of heterogeneity. At last, publication bias was determined by Deek\u0026rsquo; regression test. P value \u0026lt; 0.05 was considered to be statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eStudy selection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eRunning the systematic search, a total of 121 citations were found: 35 in PubMed, 61 in Embase, 0 in Cochrane Library, 11 in Web of Science, and 14 in CNKI, respectively. As depicted in the flowchart (\u003cstrong\u003eFigure 1\u003c/strong\u003e), 20 duplicate records were removed. Furthermore, after scanning the titles and abstracts, 83 records were discarded because they were irrelevant studies, abstracts, books, letters, meetings, or comments. Subsequently, 18 studies were identified for full-text reading. After reading the full-text of the 18 studies, 10 studies were excluded for the following reasons: two were not about cancer[\u003ca href=\"#_ENREF_24\"\u003e24\u003c/a\u003e, \u003ca href=\"#_ENREF_25\"\u003e25\u003c/a\u003e], five did not refer to circulating PTX3[\u003ca href=\"#_ENREF_26\"\u003e26-30\u003c/a\u003e], two articles did not report the diagnostic performance of circulating PTX3 in cancer detection[\u003ca href=\"#_ENREF_31\"\u003e31\u003c/a\u003e, \u003ca href=\"#_ENREF_32\"\u003e32\u003c/a\u003e], one paper did not present sufficient data[\u003ca href=\"#_ENREF_33\"\u003e33\u003c/a\u003e]. Finally, eight papers involving nine studies were included in this meta-analysis[\u003ca href=\"#_ENREF_12\"\u003e12-16\u003c/a\u003e, \u003ca href=\"#_ENREF_34\"\u003e34-36\u003c/a\u003e].\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudies characteristics\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe main features of the nine included studies, such as name of the first author, year of publication, country, cancer type, number of patients and controls, sensitivity and specificity, are presented in \u003cstrong\u003eTable 1 \u003c/strong\u003eby descending order of publication year. The included studies enrolled a total of 1408 cancer patients and 3116 control individuals. Among these studies, six were conducted in China[\u003ca href=\"#_ENREF_12\"\u003e12\u003c/a\u003e, \u003ca href=\"#_ENREF_15\"\u003e15\u003c/a\u003e, \u003ca href=\"#_ENREF_34\"\u003e34-36\u003c/a\u003e], two in Italy[\u003ca href=\"#_ENREF_13\"\u003e13\u003c/a\u003e, \u003ca href=\"#_ENREF_14\"\u003e14\u003c/a\u003e], and one in USA[\u003ca href=\"#_ENREF_16\"\u003e16\u003c/a\u003e]. Besides, six researches investigated the diagnostic value of PTX3 for lung cancer, and one for gastric cancer, colorectal cancer and prostate cancer, each. The publication date of the included studies rang from 2011 to 2019. All these studies used the method of enzyme linked immunosorbent assay (ELISA) to detect the serum level of PTX3.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eQuality assessment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTo assess the quality of these nine eligible studies, a graph of risk of bias and applicability concerns was drawn. As shown in \u003cstrong\u003eFigure 2\u003c/strong\u003e, only one study[\u003ca href=\"#_ENREF_13\"\u003e13\u003c/a\u003e] conformed to all the quality assessment items, and the bias of the eligible studies was mainly focused on \u0026ldquo;patients selection\u0026rdquo; and \u0026ldquo;index test\u0026rdquo;. Specially, in the domain of patient selection, 5 studies[\u003ca href=\"#_ENREF_12\"\u003e12\u003c/a\u003e, \u003ca href=\"#_ENREF_14\"\u003e14-16\u003c/a\u003e] did not state whether the study avoided inappropriate exclusions. Meanwhile, in the domain of index test, 6 studies[\u003ca href=\"#_ENREF_14\"\u003e14\u003c/a\u003e, \u003ca href=\"#_ENREF_15\"\u003e15\u003c/a\u003e, \u003ca href=\"#_ENREF_34\"\u003e34-36\u003c/a\u003e] did not adopt blinded method and one study[\u003ca href=\"#_ENREF_12\"\u003e12\u003c/a\u003e] was unclear if blinded method was used. Generally, all the included nine studies could be considered to be of upper quality.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eDiagnostic accuracy analysis\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSignificant heterogeneity in sensitivity (I\u003csup\u003e2 \u003c/sup\u003e= 83%) and specificity (I\u003csup\u003e2 \u003c/sup\u003e= 87.4%) was observed. Therefore, a random effects model was adopted in this meta-analysis to assess the diagnostic accuracy of PTX3 in cancer screening. Shown in \u003cstrong\u003eFigure 3\u003c/strong\u003e, the global sensitivity (SE) was 0.70 (95% confidence interval (CI): 0.67 \u0026ndash; 0.72) , and the specificity (SP) was 0.77 (95% CI: 0.75 \u0026ndash; 0.78). The pooled positive likelihood ratio (PLR), negative likelihood ratio (NLR), and the diagnostic odds ratio (DOR) were 2.86 (95% CI: 2.29 \u0026ndash; 3.56), 0.40 (95% CI: 0.32 \u0026ndash; 0.50) and 7.38 (95% CI: 5.05 \u0026ndash; 10.78), respectively (\u003cstrong\u003eFigure 4 and Figure 5\u003c/strong\u003e). The area under the summary receiver operator characteristic (SROC) curve was 0.80 (95% CI: 0.76 \u0026ndash; 0.83) (\u003cstrong\u003eFigure 6\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThreshold effect analysis and Heterogeneity exploration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eSpearman\u0026rsquo;s rank correlation analysis was carried out to evaluate the heterogeneity caused by threshold effect between the included studies (run on MetaDisc, version 1.4). Spearman correlation coefficient was -0.233 and the \u003cem\u003eP-\u003c/em\u003evalue was 0.546 (p \u0026gt; 0.05), indicating that threshold effect was not the source of heterogeneity in this study. Nevertheless, heterogeneity indeed existed as the I\u003csup\u003e2\u003c/sup\u003e of SE and SP were 83% and 87.4%, separately. Thereupon, meta-regression analysis was conducted to explore the sources of heterogeneity (performed on MetaDisc, version 1.4). We considered etnnicity, assay kit, sample size, and cancer type as the most possible factors causing heterogeneity. However, no satisfactory clues were observed. The results of meta-regression analysis are listed in \u003cstrong\u003eTable 2\u003c/strong\u003e.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePublication bias\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDeeks\u0026rsquo; funnel plot asymmetry analsysis (tested with STATA, version 12.0) was run to assess the potential bias between the nine eligible studies. As shown in \u003cstrong\u003eFigure 7\u003c/strong\u003e, no indication of publication bias was observed (t = 0.46; p \u0026gt; 0.05).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThough traditional surgical specimens or biopsy tissues and imaging techniques are used in the cancer diagnosis, limitations still exist mainly due to the invasive procedures and the delayed reflection of tumor dynamic changes. Besides, cancer patients are usually found at the relatively late stages and the outcome is generally poor. Therefore, it is urgent to develop new methods with high performance for cancer diagnosis using minimally invasive procedures. PTX3, also named TSG14, has been known as a candidate novel marker of inflammation[\u003ca href=\"#_ENREF_37\"\u003e37\u003c/a\u003e], especially cancer-related inflammation[\u003ca href=\"#_ENREF_38\"\u003e38\u003c/a\u003e, \u003ca href=\"#_ENREF_39\"\u003e39\u003c/a\u003e]. PTX3 involves in many crucial biological events, including cellular proliferation, angiogenesis, apoptosis, cancer cell invasion and metastasis[\u003ca href=\"#_ENREF_8\"\u003e8\u003c/a\u003e, \u003ca href=\"#_ENREF_40\"\u003e40\u003c/a\u003e]. Recent studies suggested PTX3 could be a potential serum biomarker for cancer screening[\u003ca href=\"#_ENREF_12\"\u003e12-16\u003c/a\u003e]. However, to the best of our knowledge, there is no systematic evidence-based evaluation for PTX3 as a tumor marker in cancer detection. In this study, we performed a systematic review and meta-analysis to assess the diagnostic performance of circulating PTX3 in cancer diagnosis.\u003c/p\u003e\n\u003cp\u003eIn this meta-analysis, a total of eight papers with 4524 individuals (1408 cancer patients and 3116 controls) were enrolled. Pooling the data from the included studies presented a combined SE of 0.70 (95% CI: 0.67 \u0026ndash; 0.72) and a combined SP of 0.77 (95% CI: 0.75 \u0026ndash; 0.78). Diagnostic odds ratio (DOR), a merged power of SE and SP, is a metric of overall diagnostic performance. A higher DOR, a better diagnostic accracy. The global DOR of PTX3 in this study is 7.38 (95% CI: 5.05 \u0026ndash; 10.78), implying that PTX3 was of good diagnostic performance in cancer screening. To further investigate the diagnostic performance, we drew the SROC curve and calculated the corresponding AUC. Generally speaking, an AUC value of 0.75 to 0.92 means a good overall diagnostic performance, 0.92 to 0.96 means very good , and 0.97 to 1 means excellent[\u003ca href=\"#_ENREF_41\"\u003e41\u003c/a\u003e, \u003ca href=\"#_ENREF_42\"\u003e42\u003c/a\u003e]. The AUC of SROC curve for PTX3 was 0.8 (95% CI: 0.76 \u0026ndash; 0.83), suggesting a good diagnostic accuracy. All of these results imply that PTX3 could be a novel promising diagnostic biomarker in cancer detection.\u003c/p\u003e\n\u003cp\u003eOur study has several advantages. Firstly, the computerised search did not involve any language restriction on the publications in order to enroll more suitable studies besides english version. Secondly, our study is the first systematic review to verify the overall diagnostic accuracy of circulating PTX3 in cancer screening. Thirdly, PTX3 could be a potential biomarker for cancer with minimal invasiveness comparing to bioscopy and pathological examination.\u003c/p\u003e\n\u003cp\u003eHowever, our study also has some weaknesses. At first, though meticulous comprehensive search was carried out in PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure (CNKI), only nine eligible studies were included in this meta-analysis. Besides, substantial heterogeneity in sensitivity (I\u003csup\u003e2 \u003c/sup\u003e= 83%) and specificity (I\u003csup\u003e2 \u003c/sup\u003e= 87.4%) exists between the included studies. According to the results of Spearman\u0026rsquo;s rank correlation analysis (Spearman coefficient = -0.233, p value = 0.546 ), threshold effect was not the source of heterogeneity. Furthermore, we conducted meta-regression analysis to identify the factor(s) causing heterogeneity. Several covariates, like etnnicity, assay kit, sample size, and cancer type were adopted as the most possible source(s) of heterogeneity. Unfortunately, no statistical significant evidence was obtained. What\u0026rsquo;s more, although there was no significant publication bias among the studies presented by Deeks\u0026rsquo; funnel plot asymmetry analsysis (\u003cstrong\u003eFigure 7\u003c/strong\u003e), some latent bias may still exists because positive results are likely to be reported.\u003c/p\u003e"},{"header":"Conclusions","content":"In conclusion, this systematic review and meta-analysis provide convincing evidence that PTX3 is of considerable diagnostic accuracy and may be a potential biomarker in cancer detection. However, as the current diagnostic data are limited, more multicenter, well-designed high quality trials with large sample size should be done to strengthen the theory of PTX3 in cancer diagnosis."},{"header":"Abbreviations","content":"\u003cp\u003ePTX3: pentraxin 3; GC: gastric cancer; CRC: colorectal cancer; LC: lung cancer; PC: prostate cancer; N: number; NR: not report; CNKI: Chinese National Knowledge Infrastructure; SE: sensitivity; SP: specificity; PLR: positive likelihood ratio; NLR: negative likelihood ratio; DOR: diagnostic odds ratio; SROC: summary receiver operator characteristic; AUC: area under curve; TP: true positive; FP: false positive; TN: true negative; FN: false negative; ELISA: enzyme linked immunosorbent assay; PRISMA: preferred reporting items for systematic reviews and meta-analysis; QUADAS-2: quality assessment of diagnostic accuracy studies 2.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNA\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eChangguo Gu designed this systematic review and meta-analysis; Qindong Liang and Guangjie Zhang carried out the literature search and drafted the manuscript; Qindong Liang, Guangjie Zhang and Huaan Huang analyzed the data; Nai Xing, Shangchun Sheng and Changguo Gu were involved in revising the manuscript; all the authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the Youth Science Fund Project of National Nature Science Foundation of China (\u003cstrong\u003eNO.\u003c/strong\u003e81702101).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData and materials are available upon request.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Ethics committee of Affiliated Hospital \u0026amp; Clinical Medical College of Chengdu University. The patients enrolled\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor details\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e1\u003c/sup\u003eDepartment of Clinical Laboratory, Affiliated Hospital \u0026amp; Clinical Medical College of Chengdu University, No.82 North Second Section Second Ring Road, Jin-Niu District, Chengdu, Sichuan 610081 China; \u003csup\u003e2\u003c/sup\u003eDepartment of Clinical Laboratory, Chengdu Fifth People\u0026rsquo;s Hospital, No. 33 Mashi Street, Wenjiang District, Chengdu, Sichuan 611130, China\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eMcGuire S: \u003cstrong\u003eWorld Cancer Report 2014. Geneva, Switzerland: World Health Organization, International Agency for Research on Cancer, WHO Press, 2015\u003c/strong\u003e. \u003cem\u003eAdvances in Nutrition \u003c/em\u003e2016, \u003cstrong\u003e7\u003c/strong\u003e(2):418-419.\u003c/li\u003e\n\u003cli\u003eGupta AK, Brenner DE, Turgeon DK: \u003cstrong\u003eEarly detection of colon cancer: new tests on the horizon\u003c/strong\u003e. \u003cem\u003eMolecular diagnosis \u0026amp; therapy \u003c/em\u003e2008, \u003cstrong\u003e12\u003c/strong\u003e(2):77-85.\u003c/li\u003e\n\u003cli\u003eKelsen DP, Ginsberg R, Pajak TF, Sheahan DG, Gunderson L, Mortimer J, Estes N, Haller DG, Ajani J, Kocha W\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eChemotherapy followed by surgery compared with surgery alone for localized esophageal cancer\u003c/strong\u003e. \u003cem\u003eThe New England journal of medicine \u003c/em\u003e1998, \u003cstrong\u003e339\u003c/strong\u003e(27):1979-1984.\u003c/li\u003e\n\u003cli\u003ePortenoy RK, Thaler HT, Kornblith AB, Lepore JM, Friedlander-Klar H, Coyle N, Smart-Curley T, Kemeny N, Norton L, Hoskins W\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eSymptom prevalence, characteristics and distress in a cancer population\u003c/strong\u003e. \u003cem\u003eQuality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation \u003c/em\u003e1994, \u003cstrong\u003e3\u003c/strong\u003e(3):183-189.\u003c/li\u003e\n\u003cli\u003eMahadevia PJ, Fleisher LA, Frick KD, Eng J, Goodman SN, Powe NR: \u003cstrong\u003eLung cancer screening with helical computed tomography in older adult smokers: a decision and cost-effectiveness analysis\u003c/strong\u003e. \u003cem\u003eJama \u003c/em\u003e2003, \u003cstrong\u003e289\u003c/strong\u003e(3):313-322.\u003c/li\u003e\n\u003cli\u003eGanti AK, Mulshine JL: \u003cstrong\u003eLung cancer screening\u003c/strong\u003e. \u003cem\u003eThe oncologist \u003c/em\u003e2006, \u003cstrong\u003e11\u003c/strong\u003e(5):481-487.\u003c/li\u003e\n\u003cli\u003eAberle DR, Adams AM, Berg CD, Black WC, Clapp JD, Fagerstrom RM, Gareen IF, Gatsonis C, Marcus PM, Sicks JD: \u003cstrong\u003eReduced lung-cancer mortality with low-dose computed tomographic screening\u003c/strong\u003e. \u003cem\u003eThe New England journal of medicine \u003c/em\u003e2011, \u003cstrong\u003e365\u003c/strong\u003e(5):395-409.\u003c/li\u003e\n\u003cli\u003eBaruah P, Dumitriu IE, Peri G, Russo V, Mantovani A, Manfredi AA, Rovere-Querini P: \u003cstrong\u003eThe tissue pentraxin PTX3 limits C1q-mediated complement activation and phagocytosis of apoptotic cells by dendritic cells\u003c/strong\u003e. \u003cem\u003eJournal of leukocyte biology \u003c/em\u003e2006, \u003cstrong\u003e80\u003c/strong\u003e(1):87-95.\u003c/li\u003e\n\u003cli\u003eMantovani A, Garlanda C, Bottazzi B: \u003cstrong\u003ePentraxin 3, a non-redundant soluble pattern recognition receptor involved in innate immunity\u003c/strong\u003e. \u003cem\u003eVaccine \u003c/em\u003e2003, \u003cstrong\u003e21 Suppl 2\u003c/strong\u003e:S43-47.\u003c/li\u003e\n\u003cli\u003eGarlanda C, Bottazzi B, Bastone A, Mantovani A: \u003cstrong\u003ePentraxins at the crossroads between innate immunity, inflammation, matrix deposition, and female fertility\u003c/strong\u003e. \u003cem\u003eAnnual review of immunology \u003c/em\u003e2005, \u003cstrong\u003e23\u003c/strong\u003e:337-366.\u003c/li\u003e\n\u003cli\u003eLin Q, Fu F, Shen L, Zhu B: \u003cstrong\u003ePentraxin 3 in the assessment of ventilator-associated pneumonia: an early marker of severity\u003c/strong\u003e. \u003cem\u003eHeart \u0026amp; lung : the journal of critical care \u003c/em\u003e2013, \u003cstrong\u003e42\u003c/strong\u003e(2):139-145.\u003c/li\u003e\n\u003cli\u003eLiu B, Zhao Y, Guo L: \u003cstrong\u003eIncreased serum pentraxin-3 level predicts poor prognosis in patients with colorectal cancer after curative surgery, a cohort study\u003c/strong\u003e. \u003cem\u003eMedicine \u003c/em\u003e2018, \u003cstrong\u003e97\u003c/strong\u003e(40):e11780.\u003c/li\u003e\n\u003cli\u003eInfante M, Allavena P, Garlanda C, Nebuloni M, Morenghi E, Rahal D, Roncalli M, Cavuto S, Pesce S, Monari M\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003ePrognostic and diagnostic potential of local and circulating levels of pentraxin 3 in lung cancer patients\u003c/strong\u003e. \u003cem\u003eInternational journal of cancer \u003c/em\u003e2016, \u003cstrong\u003e138\u003c/strong\u003e(4):983-991.\u003c/li\u003e\n\u003cli\u003eStallone G, Cormio L, Netti GS, Infante B, Selvaggio O, Fino GD, Ranieri E, Bruno F, Prattichizzo C, Sanguedolce F\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003ePentraxin 3: a novel biomarker for predicting progression from prostatic inflammation to prostate cancer\u003c/strong\u003e. \u003cem\u003eCancer research \u003c/em\u003e2014, \u003cstrong\u003e74\u003c/strong\u003e(16):4230-4238.\u003c/li\u003e\n\u003cli\u003eZhang D, Ren WH, Gao Y, Wang NY, Wu WJ: \u003cstrong\u003eClinical significance and prognostic value of pentraxin-3 as serologic biomarker for lung cancer\u003c/strong\u003e. \u003cem\u003eAsian Pacific journal of cancer prevention : APJCP \u003c/em\u003e2013, \u003cstrong\u003e14\u003c/strong\u003e(7):4215-4221.\u003c/li\u003e\n\u003cli\u003eDiamandis EP, Goodglick L, Planque C, Thornquist MD: \u003cstrong\u003ePentraxin-3 is a novel biomarker of lung carcinoma\u003c/strong\u003e. \u003cem\u003eClinical cancer research : an official journal of the American Association for Cancer Research \u003c/em\u003e2011, \u003cstrong\u003e17\u003c/strong\u003e(8):2395-2399.\u003c/li\u003e\n\u003cli\u003eDi Caro G, Carvello M, Pesce S, Erreni M, Marchesi F, Todoric J, Sacchi M, Montorsi M, Allavena P, Spinelli A: \u003cstrong\u003eCirculating Inflammatory Mediators as Potential Prognostic Markers of Human Colorectal Cancer\u003c/strong\u003e. \u003cem\u003ePloS one \u003c/em\u003e2016, \u003cstrong\u003e11\u003c/strong\u003e(2):e0148186.\u003c/li\u003e\n\u003cli\u003eSong T, Wang C, Guo C, Liu Q, Zheng X: \u003cstrong\u003ePentraxin 3 overexpression accelerated tumor metastasis and indicated poor prognosis in hepatocellular carcinoma via driving epithelial-mesenchymal transition\u003c/strong\u003e. \u003cem\u003eJournal of Cancer \u003c/em\u003e2018, \u003cstrong\u003e9\u003c/strong\u003e(15):2650-2658.\u003c/li\u003e\n\u003cli\u003eKondo S, Ueno H, Hosoi H, Hashimoto J, Morizane C, Koizumi F, Tamura K, Okusaka T: \u003cstrong\u003eClinical impact of pentraxin family expression on prognosis of pancreatic carcinoma\u003c/strong\u003e. \u003cem\u003eBritish journal of cancer \u003c/em\u003e2013, \u003cstrong\u003e109\u003c/strong\u003e(3):739-746.\u003c/li\u003e\n\u003cli\u003eMoher D, Liberati A, Tetzlaff J, Altman DG: \u003cstrong\u003ePreferred reporting items for systematic reviews and meta-analyses: the PRISMA statement\u003c/strong\u003e. \u003cem\u003eAnn Intern Med \u003c/em\u003e2009, \u003cstrong\u003e151\u003c/strong\u003e(4):264-269, W264.\u003c/li\u003e\n\u003cli\u003ePage MJ, Moher D: \u003cstrong\u003eEvaluations of the uptake and impact of the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) Statement and extensions: a scoping review\u003c/strong\u003e. \u003cem\u003eSyst Rev \u003c/em\u003e2017, \u003cstrong\u003e6\u003c/strong\u003e(1):263.\u003c/li\u003e\n\u003cli\u003eWhiting PF, Rutjes AW, Westwood ME, Mallett S, Deeks JJ, Reitsma JB, Leeflang MM, Sterne JA, Bossuyt PM: \u003cstrong\u003eQUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies\u003c/strong\u003e. \u003cem\u003eAnn Intern Med \u003c/em\u003e2011, \u003cstrong\u003e155\u003c/strong\u003e(8):529-536.\u003c/li\u003e\n\u003cli\u003eZamora J, Abraira V, Muriel A, Khan K, Coomarasamy A: \u003cstrong\u003eMeta-DiSc: a software for meta-analysis of test accuracy data\u003c/strong\u003e. \u003cem\u003eBMC Med Res Methodol \u003c/em\u003e2006, \u003cstrong\u003e6\u003c/strong\u003e:31.\u003c/li\u003e\n\u003cli\u003eOzsu S, Abul Y, Mentese A, Bektas H, Uzun A, Ozlu T: \u003cstrong\u003ePentraxin-3: A novel biomarker for the differentiation of parapneumonic effusion and malignant pleural effusion\u003c/strong\u003e. \u003cem\u003eEuropean Respiratory Journal \u003c/em\u003e2012, \u003cstrong\u003e40\u003c/strong\u003e((Ozsu S.; Abul Y.; Mentese A.; Bektas H.; Uzun A.; Ozlu T.)).\u003c/li\u003e\n\u003cli\u003eZhou X, Kang F, Wang S, Wang J: \u003cstrong\u003eDiagnosis efficacy of plasma PTX3 under the guidance of 18F-FDG PET/CT in patients with Takayasu's arteritis\u003c/strong\u003e. \u003cem\u003eJournal of Nuclear Medicine \u003c/em\u003e2017, \u003cstrong\u003e58\u003c/strong\u003e((Kang F.) Xi'An, China).\u003c/li\u003e\n\u003cli\u003eLiu C, Yao Y, Wang W: \u003cstrong\u003ePentraxin-3 as a prognostic marker in patients with small-cell lung cancer\u003c/strong\u003e. \u003cem\u003eMed Oncol \u003c/em\u003e2014, \u003cstrong\u003e31\u003c/strong\u003e(10):014-0207.\u003c/li\u003e\n\u003cli\u003eLocatelli M, Ferrero S, Martinelli Boneschi F, Boiocchi L, Zavanone M, Maria Gaini S, Bello L, Valentino S, Barbati E, Nebuloni M\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eThe long pentraxin PTX3 as a correlate of cancer-related inflammation and prognosis of malignancy in gliomas\u003c/strong\u003e. \u003cem\u003eJournal of neuroimmunology \u003c/em\u003e2013, \u003cstrong\u003e260\u003c/strong\u003e(1-2):99-106.\u003c/li\u003e\n\u003cli\u003eMiyake M, Goodison S, Chang M, Dai Y, Urquidi V, Rosser CJ: \u003cstrong\u003eA multi-analyte assay for the noninvasive detection of bladder cancer\u003c/strong\u003e. \u003cem\u003eJournal of Clinical Oncology \u003c/em\u003e2013, \u003cstrong\u003e31\u003c/strong\u003e(6).\u003c/li\u003e\n\u003cli\u003ePeng X, Xue H, L\u0026uuml; L, Shi P, Wang J: \u003cstrong\u003eAccumulated promoter methylation as a potential biomarker for esophageal cancer\u003c/strong\u003e. \u003cem\u003eOncotarget \u003c/em\u003e2017, \u003cstrong\u003e8\u003c/strong\u003e(1):679-691.\u003c/li\u003e\n\u003cli\u003eUrquidi V, Goodison S, Ross S, Chang M, Dai Y, Rosser CJ: \u003cstrong\u003eDiagnostic potential of urinary \u0026alpha;1-antitrypsin and apolipoprotein e in the detection of bladder cancer\u003c/strong\u003e. \u003cem\u003eJournal of Urology \u003c/em\u003e2012, \u003cstrong\u003e188\u003c/strong\u003e(6):2377-2383.\u003c/li\u003e\n\u003cli\u003eTakeda N, Asai K, Ijiri N, Yamamoto N, Watanabe T, Kamoi H, Kanazawa H, Hirata K: \u003cstrong\u003ePentraxin-3 as a Biomarker for Febrile Neutropenia in Patients with Lung Cancer\u003c/strong\u003e. \u003cem\u003eOsaka city medical journal \u003c/em\u003e2015, \u003cstrong\u003e61\u003c/strong\u003e(1):43-52.\u003c/li\u003e\n\u003cli\u003eZhang J, Wang TY, Niu XC: \u003cstrong\u003eIncreased Plasma Levels of Pentraxin 3 Are Associated with Poor Prognosis of Colorectal Carcinoma Patients\u003c/strong\u003e. \u003cem\u003eThe Tohoku journal of experimental medicine \u003c/em\u003e2016, \u003cstrong\u003e240\u003c/strong\u003e(1):39-46.\u003c/li\u003e\n\u003cli\u003eGoodison S, Chang M, Dai Y, Urquidi V, Rosser CJ: \u003cstrong\u003eA Multi-Analyte Assay for the Non-Invasive Detection of Bladder Cancer\u003c/strong\u003e. \u003cem\u003ePloS one \u003c/em\u003e2012, \u003cstrong\u003e7\u003c/strong\u003e(10).\u003c/li\u003e\n\u003cli\u003eChen L: \u003cstrong\u003eApplication value of serum Pentraxin-3 in diagnosis of gastric cancer\u003c/strong\u003e. \u003cem\u003eLaboratory Medicine and Clinic \u003c/em\u003e2019(03):343-346.\u003c/li\u003e\n\u003cli\u003eLu K: \u003cstrong\u003eThe diagnostic value of the levels of CYFRA21-1, Pentraxin-3, ProGRP for non-small cell lung cancer\u003c/strong\u003e. \u003cem\u003eChina Journal of Laboratory Diagnosis \u003c/em\u003e2016(03):378-380.\u003c/li\u003e\n\u003cli\u003eXu JZ, H: \u003cstrong\u003eThe value of serum pentraxin-3 combined with HE4 in NSCLC diagnosis and prognosis \u003c/strong\u003e\u003cem\u003eChinese Journal of Clinical Laboratory Science \u003c/em\u003e2015, \u003cstrong\u003e33\u003c/strong\u003e(04):282-284.\u003c/li\u003e\n\u003cli\u003eOzsu S, Abul Y, Mentese A, Bektas H, Uzun A, Ozlu T, Porcel JM: \u003cstrong\u003ePentraxin-3: A novel biomarker for discriminating parapneumonic from other exudative effusions\u003c/strong\u003e. \u003cem\u003eRespirology \u003c/em\u003e2013, \u003cstrong\u003e18\u003c/strong\u003e(4):657-662.\u003c/li\u003e\n\u003cli\u003eGermano G, Frapolli R, Simone M, Tavecchio M, Erba E, Pesce S, Pasqualini F, Grosso F, Sanfilippo R, Casali PG\u003cem\u003e et al\u003c/em\u003e: \u003cstrong\u003eAntitumor and anti-inflammatory effects of trabectedin on human myxoid liposarcoma cells\u003c/strong\u003e. \u003cem\u003eCancer research \u003c/em\u003e2010, \u003cstrong\u003e70\u003c/strong\u003e(6):2235-2244.\u003c/li\u003e\n\u003cli\u003eLai CS, Li S, Chai CY, Lo CY, Dushenkov S, Ho CT, Pan MH, Wang YJ: \u003cstrong\u003eAnti-inflammatory and antitumor promotional effects of a novel urinary metabolite, 3',4'-didemethylnobiletin, derived from nobiletin\u003c/strong\u003e. \u003cem\u003eCarcinogenesis \u003c/em\u003e2008, \u003cstrong\u003e29\u003c/strong\u003e(12):2415-2424.\u003c/li\u003e\n\u003cli\u003eRutkowski MJ, Sughrue ME, Kane AJ, Mills SA, Parsa AT: \u003cstrong\u003eCancer and the complement cascade\u003c/strong\u003e. \u003cem\u003eMolecular cancer research : MCR \u003c/em\u003e2010, \u003cstrong\u003e8\u003c/strong\u003e(11):1453-1465.\u003c/li\u003e\n\u003cli\u003eSwets JA: \u003cstrong\u003eMeasuring the accuracy of diagnostic systems\u003c/strong\u003e. \u003cem\u003eScience \u003c/em\u003e1988, \u003cstrong\u003e240\u003c/strong\u003e(4857):1285-1293.\u003c/li\u003e\n\u003cli\u003eJones CM, Athanasiou T: \u003cstrong\u003eSummary receiver operating characteristic curve analysis techniques in the evaluation of diagnostic tests\u003c/strong\u003e. \u003cem\u003eThe Annals of thoracic surgery \u003c/em\u003e2005, \u003cstrong\u003e79\u003c/strong\u003e(1):16-20.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\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":"pentraxin 3; cancer; diagnosis; meta-analysis","lastPublishedDoi":"10.21203/rs.2.16075/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.2.16075/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground Mounting studies reported that circulating pentraxin 3 (PTX3) expression level was significantly different between cancer patients and healthy groups, suggesting that PTX3 may be a potential biomarker for cancer detection. However, the results were inconsistent. In this paper, a systematic review and meta-analysis was performed to quantitatively assess the diagnostic value of PTX3 in cancer detection.Methods A comprehensive computerized literature search was conducted in Embase, PubMed, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure (CNKI) from inception to July 31, 2019. Eligible studies were identified and raw data were extracted. Diagnostic estimates were synthesized using STATA (version 12.0) and MetaDisc (version 1.4) statistical software.Results Overall, 9 studies from 8 citations with a total of 1408 cancer patiens and 3116 controls were included in this meta-analysis. The global sensitivity was 0.70 (95% confidence interval (CI): 0.67 – 0.72), and the specificity was 0.77 (95% CI: 0.75 – 0.78). The pooled positive likelihood ratio (PLR), negative likelihood ratio (NLR), and the diagnostic odds ratio (DOR) were 2.86 (95% CI: 2.29 – 3.56), 0.40 (95% CI: 0.32 – 0.50) and 7.38 (95% CI: 5.05 – 10.78), respectively. The merged AUC was 0.80 (95% CI: 0.76 – 0.83).Conclusion The serum PTX3 appears to be a reliable biomarker for cancer detection though large-scale multicenter studies are needed.\u003c/p\u003e","manuscriptTitle":"Pentraxin 3 as a promising biomarker for cancer detection: a systematic review and meta-analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2019-10-15 23:07:06","doi":"10.21203/rs.2.16075/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":"320dfd2d-7226-4a56-9eb1-4f8399c97bd0","owner":[],"postedDate":"October 15th, 2019","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":32093,"name":"Cancer Biology"},{"id":32094,"name":"Oncology"}],"tags":[],"updatedAt":"","versionOfRecord":[],"versionCreatedAt":"2019-10-15 23:07:06","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6730","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"identity":"rs-6730","version":["v1"]},"buildId":"-HB7Z8yhvgn0wM9Nzuekk","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}