{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T18:11:07Z","timestamp":1789582267224,"version":"build-2803163510"},"reference-count":39,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T00:00:00Z","timestamp":1762214400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"\n Background<\/jats:title>\n \n Pepsinogen (PG) and gastrin-17 (G-17) are widely used in the screening of gastric diseases. Our cross-sectional clinical study investigates the relationship between\n Helicobacter pylori<\/jats:italic>\n (HP) infection, sex, and age on serum levels of PG and G-17 in asymptomatic subjects in Rizhao, China.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n A total of 12,746 asymptomatic subjects were enrolled in the study between August 2023 and January 2024. Serum levels of pepsinogen I (PGI), pepsinogen II (PGII), and G-17 were measured using the chemiluminescent microparticle immunoassay method, and the PGI\/PGII ratio (PGR) was calculated. HP infection was detected using the Colloidal Gold Method, and the relationship between age, sex, HP infection, and serum PG and G-17 levels was analyzed.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n HP prevalence was 19.33% in this study. The serum PGI, PGII, and G-17 levels were significantly higher in the HP-positive group compared to the HP-negative group (P\u2009<\u20090.001), whereas the PGR was notably lower in the HP-positive group (P\u2009<\u20090.001). Spearman correlation tests analysis indicated a positive correlation between HP infection and PGI, PGII, and G-17 (r\u2009=\u20090.144, P\u2009<\u20090.001; r\u2009=\u20090.418, P\u2009<\u20090.001; r\u2009=\u20090.268, P\u2009<\u20090.001), and a negative correlation with PGR (r\u2009=\u2009\u22120.438, P\u2009<\u20090.001). ROC curve shows that the AUC of the combination of PGI, PGII, PGR, and G-17 in diagnosing HP positive were 0.605 (95% CI: 0.592\u20130.618), 0.805 (95% CI: 0.795\u20130.816), 0.820 (95% CI: 0.811\u20130.830), and 0.709 (95% CI: 0.698\u20130.720), respectively. The detection rates of abnormal PG and G-17 levels were significantly higher in the HP-positive group than in the HP-negative group (P\u2009<\u20090.01). Males exhibited significantly higher levels of both PGI and PGII than females (P\u2009<\u20090.001). The G-17 levels were higher in males than females in the 50\u201359 age group (P\u2009<\u20090.05). Spearman correlation analysis revealed that serum levels of both PGI and PGII exhibited an increase with age. Serum PGI, PGII, and G-17 levels were positively correlated with age, although the relationship was weak (r\u2009=\u20090.228, P\u2009<\u20090.001; r\u2009=\u20090.246, P\u2009<\u20090.001; r\u2009=\u20090.042, P\u2009<\u20090.001). Following adjustment for sex and Helicobacter pylori infection covariates using a restricted cubic spline (RCS), the analysis revealed a significant overall association between PGI, PGII, PGR, and G-17 serum levels and age (P for overall\u2009<\u20090.001, P for overall\u2009<\u20090.001, P for overall\u2009=\u20090.003, and P for overall\u2009<\u20090.001, respectively). Furthermore, a nonlinear relationship was found between PGI, PGR, and G-17 levels and age (nonlinear P\u2009=\u20090.004, nonlinear P\u2009=\u20090.001, and nonlinear P\u2009=\u20090.008, respectively), whereas PGII exhibited a linear correlation (nonlinear P\u2009=\u20090.841).<\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n Serum levels of PG and G-17 are associated with HP infection, sex, and age. These findings provide region-specific insights into the relationships between these biomarkers and HP infection, highlighting the importance of considering HP infection status, sex, and age in future research.<\/jats:p>\n <\/jats:sec>","DOI":"10.1371\/journal.pone.0335228","type":"journal-article","created":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T18:25:12Z","timestamp":1762280712000},"page":"e0335228","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Associations of serum pepsinogen and Gastrin-17 with Helicobacter pylori infection, sex, and age, in an asymptomatic coastal population: A cross-sectional study in Rizhao, China"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9654-332X","authenticated-orcid":true,"given":"Tianyi","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangxiang","family":"Meng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanwen","family":"Mi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanjie","family":"Qu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujun","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaocai","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3469-8586","authenticated-orcid":true,"given":"Mengmeng","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,11,4]]},"reference":[{"issue":"8","key":"pone.0335228.ref001","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.20892\/j.issn.2095-3941.2022.0231","article-title":"Current cancer burden in China: epidemiology, etiology, and prevention","volume":"19","author":"C Maomao","year":"2022","journal-title":"Cancer Biol Med"},{"issue":"3","key":"pone.0335228.ref002","first-page":"209","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"H Sung","year":"2021","journal-title":"CA Cancer J Clin"},{"issue":"28","key":"pone.0335228.ref003","doi-asserted-by":"crossref","first-page":"6385","DOI":"10.3748\/wjg.v22.i28.6385","article-title":"Benefits and harms of endoscopic screening for gastric cancer","volume":"22","author":"C Hamashima","year":"2016","journal-title":"World J Gastroenterol"},{"issue":"12","key":"pone.0335228.ref004","doi-asserted-by":"crossref","first-page":"1622","DOI":"10.20892\/j.issn.2095-3941.2022.0655","article-title":"Early detection of gastric cancer in China: progress and opportunities","volume":"19","author":"H Xu","year":"2022","journal-title":"Cancer Biol Med"},{"issue":"4","key":"pone.0335228.ref005","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1007\/s005350300060","article-title":"Serum pepsinogen concentration as a marker of Helicobacter pyloriinfection and the histologic grade of gastritis; evaluation of gastric mucosa by serum pepsinogen levels","volume":"38","author":"K Kiyohira","year":"2003","journal-title":"J Gastroenterol"},{"issue":"7","key":"pone.0335228.ref006","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.dld.2008.02.028","article-title":"Non-invasive tests in gastric diseases","volume":"40","author":"F di Mario","year":"2008","journal-title":"Dig Liver Dis"},{"issue":"10","key":"pone.0335228.ref007","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.1007\/s10620-006-9206-1","article-title":"Usefulness of serum pepsinogens in Helicobacter pylori chronic gastritis: relationship with inflammation, activity, and density of the bacterium","volume":"51","author":"F Di Mario","year":"2006","journal-title":"Dig Dis Sci"},{"issue":"2","key":"pone.0335228.ref008","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1002\/ijc.29005","article-title":"Temporal changes in serum biomarkers and risk for progression of gastric precancerous lesions: a longitudinal study","volume":"136","author":"H Tu","year":"2015","journal-title":"Int J Cancer"},{"issue":"1","key":"pone.0335228.ref009","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1186\/s12876-021-01794-6","article-title":"Serum pepsinogen levels in different regions of China and its influencing factors: a multicenter cross-sectional study","volume":"21","author":"Y Tong","year":"2021","journal-title":"BMC Gastroenterol"},{"key":"pone.0335228.ref010","doi-asserted-by":"crossref","first-page":"6894248","DOI":"10.1155\/2021\/6894248","article-title":"The Diagnostic Value of Serum Gastrin-17 and Pepsinogen for Gastric Cancer Screening in Eastern China","volume":"2021","author":"H Shen","year":"2021","journal-title":"Gastroenterol Res Pract"},{"issue":"4","key":"pone.0335228.ref011","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1152\/physrev.1998.78.4.1087","article-title":"The new biology of gastrointestinal hormones","volume":"78","author":"JF Rehfeld","year":"1998","journal-title":"Physiol Rev"},{"key":"pone.0335228.ref012","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1146\/annurev.physiol.63.1.49","article-title":"Gastrin, CCK, signaling, and cancer","volume":"63","author":"E Rozengurt","year":"2001","journal-title":"Annu Rev Physiol"},{"issue":"12","key":"pone.0335228.ref013","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1080\/00365520802273025","article-title":"Serum biomarkers provide an accurate method for diagnosis of atrophic gastritis in a general population: The Kalixanda study","volume":"43","author":"T Storskrubb","year":"2008","journal-title":"Scand J Gastroenterol"},{"issue":"8","key":"pone.0335228.ref014","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1097\/00042737-200308000-00009","article-title":"Non-endoscopic diagnosis of atrophic gastritis with a blood test. Correlation between gastric histology and serum levels of gastrin-17 and pepsinogen I: a multicentre study","volume":"15","author":"H V\u00e4\u00e4n\u00e4nen","year":"2003","journal-title":"Eur J Gastroenterol Hepatol"},{"issue":"19","key":"pone.0335228.ref015","doi-asserted-by":"crossref","first-page":"1607","DOI":"10.1093\/jnci\/92.19.1607","article-title":"Gastric dysplasia and gastric cancer: Helicobacter pylori, serum vitamin C, and other risk factors","volume":"92","author":"WC You","year":"2000","journal-title":"J Natl Cancer Inst"},{"issue":"4","key":"pone.0335228.ref016","doi-asserted-by":"crossref","first-page":"220","DOI":"10.4103\/sjg.SJG_486_17","article-title":"Association of coagulopathy with the risk of bleeding after invasive procedures in liver cirrhosis","volume":"24","author":"J Li","year":"2018","journal-title":"Saudi J Gastroenterol"},{"issue":"3","key":"pone.0335228.ref017","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1002\/jso.26498","article-title":"Prognostic importance of dynamic changes in systemic inflammatory markers for patients with gastric cancer","volume":"124","author":"J-X Lin","year":"2021","journal-title":"J Surg Oncol"},{"issue":"1","key":"pone.0335228.ref018","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1007\/s12672-022-00570-6","article-title":"The relationship of serum gastrin-17 and oral mucositis in head and neck carcinoma patients receiving radiotherapy","volume":"13","author":"C Wu","year":"2022","journal-title":"Discov Oncol"},{"issue":"11","key":"pone.0335228.ref019","first-page":"4951","article-title":"Gut peptide profile and chemotherapy-associated dyspepsia syndrome in patients with breast cancer undergoing FEC60 chemotherapy","volume":"33","author":"G Riezzo","year":"2013","journal-title":"Anticancer Res"},{"issue":"1","key":"pone.0335228.ref020","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.numecd.2020.07.045","article-title":"Association between serum pepsinogen and atherosclerotic cardiovascular disease","volume":"31","author":"X Gao","year":"2021","journal-title":"Nutr Metab Cardiovasc Dis"},{"key":"pone.0335228.ref021","doi-asserted-by":"crossref","first-page":"975921","DOI":"10.3389\/fimmu.2022.975921","article-title":"Gut microbes in cerebrovascular diseases: Gut flora imbalance, potential impact mechanisms and promising treatment strategies","volume":"13","author":"X Zou","year":"2022","journal-title":"Front Immunol"},{"issue":"32","key":"pone.0335228.ref022","doi-asserted-by":"crossref","first-page":"5945","DOI":"10.3748\/wjg.v23.i32.5945","article-title":"Changes with aging in gastric biomarkers levels and in biochemical factors associated with Helicobacter pylori infection in asymptomatic Chinese population","volume":"23","author":"J-H Shan","year":"2017","journal-title":"World J Gastroenterol"},{"issue":"1","key":"pone.0335228.ref023","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1136\/gut.50.1.13","article-title":"Helicobacter pylori stimulates pepsinogen secretion from isolated human peptic cells","volume":"50","author":"S Lorente","year":"2002","journal-title":"Gut"},{"issue":"1","key":"pone.0335228.ref024","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1186\/s12876-017-0641-6","article-title":"The potential value of serum pepsinogen for the diagnosis of atrophic gastritis among the health check-up populations in China: a diagnostic clinical research","volume":"17","author":"Y Tong","year":"2017","journal-title":"BMC Gastroenterol"},{"issue":"2","key":"pone.0335228.ref025","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1053\/gast.1997.v113.pm9247465","article-title":"Effect of Helicobacter pylori products and recombinant cytokines on gastrin release from cultured canine G cells","volume":"113","author":"I Beales","year":"1997","journal-title":"Gastroenterology"},{"issue":"6","key":"pone.0335228.ref026","doi-asserted-by":"crossref","DOI":"10.1152\/ajpgi.2001.281.6.G1405","article-title":"TNF-alpha and interleukin 1 activate gastrin gene expression via MAPK- and PKC-dependent mechanisms","volume":"281","author":"T Suzuki","year":"2001","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"issue":"1","key":"pone.0335228.ref027","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/s41572-023-00431-8","article-title":"Helicobacter pylori infection","volume":"9","author":"P Malfertheiner","year":"2023","journal-title":"Nat Rev Dis Primers"},{"issue":"1","key":"pone.0335228.ref028","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.canlet.2005.06.025","article-title":"Gastrin and cancer: a review","volume":"238","author":"A Ferrand","year":"2006","journal-title":"Cancer Lett"},{"issue":"4","key":"pone.0335228.ref029","doi-asserted-by":"crossref","first-page":"1305","DOI":"10.3748\/wjg.v21.i4.1305","article-title":"Accuracy of urea breath test in Helicobacter pylori infection: meta-analysis","volume":"21","author":"M Ferwana","year":"2015","journal-title":"World J Gastroenterol"},{"issue":"9","key":"pone.0335228.ref030","doi-asserted-by":"crossref","first-page":"1576","DOI":"10.1136\/gutjnl-2018-317556","article-title":"Development and validation of a prediction rule for estimating gastric cancer risk in the Chinese high-risk population: a nationwide multicentre study","volume":"68","author":"Gastrointestinal Early Cancer Prevention & Treatment Alliance of China (GECA)","year":"2019","journal-title":"Gut"},{"issue":"6","key":"pone.0335228.ref031","article-title":"Multicentre, cross-sectional surveillance of Helicobacter pylori prevalence and antibiotic resistance to clarithromycin and levofloxacin in urban China using the string test coupled with quantitative PCR","volume":"5","author":"Guangdong Center for Quality Control of Clinical Gene Testing and Study Group of Chinese Helicobacter pylori Infection and Antibiotic Resistance Rates Mapping Project (CHINAR-MAP)","year":"2024","journal-title":"Lancet Microbe"},{"issue":"43","key":"pone.0335228.ref032","doi-asserted-by":"crossref","first-page":"4636","DOI":"10.3748\/wjg.v30.i43.4636","article-title":"Prevalence of Helicobacter pylori infection in China from 2014-2023: A systematic review and meta-analysis","volume":"30","author":"L Xie","year":"2024","journal-title":"World J Gastroenterol"},{"key":"pone.0335228.ref033","doi-asserted-by":"crossref","first-page":"980399","DOI":"10.3389\/fcimb.2022.980399","article-title":"Association of serum pepsinogens and gastrin-17 with Helicobacter pylori infection assessed by urea breath test","volume":"12","author":"J-P Zhou","year":"2022","journal-title":"Front Cell Infect Microbiol"},{"issue":"6","key":"pone.0335228.ref034","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/S2468-1253(23)00070-5","article-title":"Global prevalence of Helicobacter pylori infection between 1980 and 2022: a systematic review and meta-analysis","volume":"8","author":"Y Li","year":"2023","journal-title":"Lancet Gastroenterol Hepatol"},{"issue":"27","key":"pone.0335228.ref035","article-title":"Serum pepsinogen II levels are doubled with Helicobacter pylori infection in an asymptomatic population of 40,383 Chinese subjects","volume":"100","author":"H Yu","year":"2021","journal-title":"Medicine (Baltimore)"},{"issue":"5","key":"pone.0335228.ref036","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.amjms.2016.08.005","article-title":"Serum Pepsinogen Levels Are Correlated With Age, Sex and the Level of Helicobacter pylori Infection in Healthy Individuals","volume":"352","author":"R-G Huang","year":"2016","journal-title":"Am J Med Sci"},{"issue":"10","key":"pone.0335228.ref037","doi-asserted-by":"crossref","DOI":"10.1002\/iid3.993","article-title":"Analysis of gastrin-17 and its related influencing factors in physical examination results","volume":"11","author":"J Zeng","year":"2023","journal-title":"Immun Inflamm Dis"},{"issue":"12","key":"pone.0335228.ref038","article-title":"Analysis of serum gastrin-17 and Helicobacter pylori antibody in healthy Chinese population","volume":"34","author":"W Liu","year":"2020","journal-title":"J Clin Lab Anal"},{"issue":"1","key":"pone.0335228.ref039","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1093\/labmed\/lmaa042","article-title":"Associations of Serum Pepsinogens and Helicobacter Pylori Infection with High-Sensitivity C-Reactive Protein in Medical Examination Population","volume":"52","author":"H Liu","year":"2021","journal-title":"Lab Med"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0335228","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T18:25:19Z","timestamp":1762280719000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0335228"}},"subtitle":[],"editor":[{"given":"Shaghayegh","family":"Khanmohammadi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,11,4]]},"references-count":39,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11,4]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0335228","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,4]]}}}