{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T23:34:12Z","timestamp":1788564852180,"version":"build-2803163510"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No. 82404341"],"award-info":[{"award-number":["No. 82404341"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["No. 32300974"],"award-info":[{"award-number":["No. 32300974"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Healthy Zhejiang One Million People Cohort","award":["K-20230085"],"award-info":[{"award-number":["K-20230085"]}]},{"name":"Zhejiang Key Laboratory of Prevention, Diagnosis and Therapy for Gastrointestinal Cancer","award":["Zhejiang Key Laboratory of Prevention, Diagnosis and Therapy for Gastrointestinal Cancer"],"award-info":[{"award-number":["Zhejiang Key Laboratory of Prevention, Diagnosis and Therapy for Gastrointestinal Cancer"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Gastric Cancer"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Accurate identification of individuals at high risk of gastric cancer (GC) remains a major challenge for effective screening. We aimed to identify plasma proteomic signatures and develop a risk prediction model for GC risk stratification.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Plasma proteomic profiling was performed using liquid chromatography\u2013tandem mass spectrometry in a case\u2013control discovery set (100 GC cases and 94 controls). Candidate proteins were evaluated in 52,552 UK Biobank participants with a median follow-up of 13.63 years, during which 92 incident GC cases were identified. Risk models integrating clinical, genetic, and proteomic factors were developed using LASSO-penalized Cox regression with stability selection and internally validated using bootstrap resampling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 2306 differentially expressed proteins in discovery, 25 were replicated in validation at nominal significance (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.05) with consistent directions. Two proteins (CTSD and GGH) remained significant after false discovery rate correction. A primary proteomic model (clinical factors plus five proteins) improved discrimination versus clinical model (optimism-corrected C-index: 0.745 vs. 0.732,\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.046). Risk stratification revealed a clear GC risk gradient: hazard ratios were 6.08 (95% CI 2.15\u201317.20) for moderate-risk and 23.88 (95% CI 8.66\u201365.87) for high-risk groups. The risk score was also associated with GC risk as continuous variable (HR per standard deviation: 1.09, 95% CI 1.08\u20131.11). The 15-year cumulative incidence ranged from 0.02 to 0.56% across risk groups. Decision curve analysis indicated improved clinical utility.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Plasma proteomic signatures may improve GC risk stratification beyond traditional clinical factors and could support more targeted screening strategies. Further validation is warranted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10120-026-01749-4","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T12:11:54Z","timestamp":1778760714000},"page":"725-736","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Plasma proteomic signatures improve risk stratification and personalized screening for gastric cancer"],"prefix":"10.1007","volume":"29","author":[{"given":"Xue","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen-Hao","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nai-Ren","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying-Ying","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang-Dong","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1992-7784","authenticated-orcid":false,"given":"Ling-Bin","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"issue":"3","key":"1749_CR1","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","volume":"74","author":"F Bray","year":"2024","unstructured":"Bray F, Laversanne M, Sung H, et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. Cancer J Clin. 2024;74(3):229\u201363.","journal-title":"Cancer J Clin"},{"issue":"1","key":"1749_CR2","first-page":"47","volume":"4","author":"B Han","year":"2024","unstructured":"Han B, Zheng R, Zeng H, et al. Cancer incidence and mortality in China, 2022. J Natl Cancer Cent. 2024;4(1):47\u201353.","journal-title":"J Natl Cancer Cent"},{"issue":"5","key":"1749_CR3","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1038\/s41571-023-00747-0","volume":"20","author":"AP Thrift","year":"2023","unstructured":"Thrift AP, Wenker TN, El-Serag HB. Global burden of gastric cancer: epidemiological trends, risk factors, screening and prevention. Nat reviews Clin Oncol. 2023;20(5):338\u201349.","journal-title":"Nat reviews Clin Oncol"},{"issue":"5","key":"1749_CR4","doi-asserted-by":"publisher","first-page":"e555","DOI":"10.1016\/S2214-109X(18)30127-X","volume":"6","author":"H Zeng","year":"2018","unstructured":"Zeng H, Chen W, Zheng R, et al. Changing cancer survival in China during 2003-15: a pooled analysis of 17 population-based cancer registries. Lancet Glob Health. 2018;6(5):e555\u201367.","journal-title":"Lancet Glob Health"},{"issue":"11","key":"1749_CR5","doi-asserted-by":"publisher","first-page":"3250","DOI":"10.1038\/s41591-024-03153-w","volume":"30","author":"K-F Pan","year":"2024","unstructured":"Pan K-F, Li W-Q, Zhang L, et al. Gastric cancer prevention by community eradication of Helicobacter pylori: a cluster-randomized controlled trial. Nat Med. 2024;30(11):3250\u201360.","journal-title":"Nat Med"},{"issue":"2","key":"1749_CR6","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1136\/gutjnl-2019-320200","volume":"70","author":"R Chen","year":"2021","unstructured":"Chen R, Liu Y, Song G, et al. Effectiveness of one-time endoscopic screening programme in prevention of upper gastrointestinal cancer in China: a multicentre population-based cohort study. Gut. 2021;70(2):251\u201360.","journal-title":"Gut"},{"issue":"4","key":"1749_CR7","doi-asserted-by":"publisher","first-page":"725","DOI":"10.1053\/j.gastro.2024.11.025","volume":"168","author":"C Xia","year":"2024","unstructured":"Xia C, Li H, Xu Y, et al. Effect of an endoscopy screening on upper gastrointestinal cancer mortality: a community-based multicenter cluster randomized clinical trial. Gastroenterology. 2024;168(4):725\u201340.","journal-title":"Gastroenterology"},{"issue":"4","key":"1749_CR8","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1093\/jnci\/djad247","volume":"116","author":"J Sun","year":"2024","unstructured":"Sun J, Luo J, Jiang F, et al. Exploring the cross-cancer effect of circulating proteins and discovering potential intervention targets for 13 site-specific cancers. J Natl Cancer Inst. 2024;116(4):565\u201373.","journal-title":"J Natl Cancer Inst"},{"issue":"1","key":"1749_CR9","doi-asserted-by":"publisher","first-page":"4010","DOI":"10.1038\/s41467-024-48017-6","volume":"15","author":"K Papier","year":"2024","unstructured":"Papier K, Atkins JR, Tong TYN, et al. Identifying proteomic risk factors for cancer using prospective and exome analyses of 1463 circulating proteins and risk of 19 cancers in the UK Biobank. Nat Commun. 2024;15(1):4010.","journal-title":"Nat Commun"},{"issue":"7982","key":"1749_CR10","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1038\/s41586-023-06592-6","volume":"622","author":"BB Sun","year":"2023","unstructured":"Sun BB, Chiou J, Traylor M, et al. Plasma proteomic associations with genetics and health in the UK Biobank. Nature. 2023;622(7982):329\u201338.","journal-title":"Nature"},{"issue":"7726","key":"1749_CR11","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1038\/s41586-018-0579-z","volume":"562","author":"C Bycroft","year":"2018","unstructured":"Bycroft C, Freeman C, Petkova D, et al. The UK Biobank resource with deep phenotyping and genomic data. Nature. 2018;562(7726):203\u20139.","journal-title":"Nature"},{"issue":"7944","key":"1749_CR12","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1038\/s41586-022-05473-8","volume":"613","author":"MI Kurki","year":"2023","unstructured":"Kurki MI, Karjalainen J, Palta P, et al. FinnGen provides genetic insights from a well-phenotyped isolated population. Nature. 2023;613(7944):508\u201318.","journal-title":"Nature"},{"issue":"9","key":"1749_CR13","doi-asserted-by":"publisher","first-page":"2489","DOI":"10.1038\/s41591-024-03142-z","volume":"30","author":"J Carrasco-Zanini","year":"2024","unstructured":"Carrasco-Zanini J, Pietzner M, Davitte J, et al. Proteomic signatures improve risk prediction for common and rare diseases. Nat Med. 2024;30(9):2489\u201398.","journal-title":"Nat Med"},{"key":"1749_CR14","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/j.matbio.2015.01.019","volume":"44\u201346","author":"G Shay","year":"2015","unstructured":"Shay G, Lynch CC, Fingleton B. Moving targets: emerging roles for MMPs in cancer progression and metastasis. Matrix Biol. 2015;44\u201346:200\u20136.","journal-title":"Matrix Biol"},{"issue":"2","key":"1749_CR15","doi-asserted-by":"publisher","first-page":"340","DOI":"10.5230\/jgc.2023.23.e19","volume":"23","author":"MQ Qiu","year":"2023","unstructured":"Qiu MQ, Wang HJ, Ju YF, et al. Fatty acid binding protein 5 (FABP5) promotes aggressiveness of gastric cancer through modulation of tumor immunity. J Gastric Cancer. 2023;23(2):340\u201354.","journal-title":"J Gastric Cancer"},{"key":"1749_CR16","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.gene.2018.07.035","volume":"676","author":"M Amiri","year":"2018","unstructured":"Amiri M, Yousefnia S, Seyed Forootan F, Peymani M, Ghaedi K, Nasr Esfahani MH. Diverse roles of fatty acid binding proteins (FABPs) in development and pathogenesis of cancers. Gene. 2018;676:171\u201383.","journal-title":"Gene"},{"issue":"6","key":"1749_CR17","doi-asserted-by":"publisher","first-page":"1172","DOI":"10.1016\/j.ajpath.2025.02.009","volume":"195","author":"L Niu","year":"2025","unstructured":"Niu L, Zhou X, Li D, Zheng Y, Li H. Glycosylation triggers cathepsin D maturation and secretion to promote gastric cancer development. Am J Pathol. 2025;195(6):1172\u201387.","journal-title":"Am J Pathol"},{"issue":"1","key":"1749_CR18","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1007\/s00432-019-03087-8","volume":"146","author":"Y Maezawa","year":"2020","unstructured":"Maezawa Y, Sakamaki K, Oue N, et al. High gamma-glutamyl hydrolase and low folylpolyglutamate synthetase expression as prognostic biomarkers in patients with locally advanced gastric cancer who were administrated postoperative adjuvant chemotherapy with S-1. J Cancer Res Clin Oncol. 2020;146(1):75\u201386.","journal-title":"J Cancer Res Clin Oncol"},{"issue":"13","key":"1749_CR19","doi-asserted-by":"publisher","first-page":"4423","DOI":"10.1158\/0008-5472.CAN-10-4157","volume":"71","author":"A Banh","year":"2011","unstructured":"Banh A, Zhang J, Cao H, et al. Tumor galectin-1 mediates tumor growth and metastasis through regulation of T-cell apoptosis. Cancer Res. 2011;71(13):4423\u201331.","journal-title":"Cancer Res"},{"issue":"1","key":"1749_CR20","doi-asserted-by":"publisher","first-page":"7566","DOI":"10.1038\/s41598-025-91066-0","volume":"15","author":"D Xu","year":"2025","unstructured":"Xu D, Zhou X, Min S, et al. Leukocyte-specific protein 1 is associated with the stage and tumor immune infiltration of cervical cancer. Sci Rep. 2025;15(1):7566.","journal-title":"Sci Rep"},{"issue":"1","key":"1749_CR21","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1007\/s12263-014-0444-0","volume":"10","author":"SE Kim","year":"2015","unstructured":"Kim SE, Hinoue T, Kim MS, et al. \u03b3-Glutamyl hydrolase modulation significantly influences global and gene-specific DNA methylation and gene expression in human colon and breast cancer cells. Genes Nutr. 2015;10(1):444.","journal-title":"Genes Nutr"},{"issue":"4","key":"1749_CR22","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1038\/s41591-022-01746-x","volume":"28","author":"RC Fitzgerald","year":"2022","unstructured":"Fitzgerald RC, Antoniou AC, Fruk L, Rosenfeld N. The future of early cancer detection. Nat Med. 2022;28(4):666\u201377.","journal-title":"Nat Med"},{"issue":"4","key":"1749_CR23","doi-asserted-by":"publisher","first-page":"675","DOI":"10.1007\/s10120-024-01488-4","volume":"27","author":"H Oh","year":"2024","unstructured":"Oh H, Cho S, Lee JA, Ryu S, Chang Y. Risk prediction model for gastric cancer within 5 years in healthy Korean adults. Gastric cancer: official J Int Gastric Cancer Association Japanese Gastric Cancer Association. 2024;27(4):675\u201383.","journal-title":"Gastric cancer: official J Int Gastric Cancer Association Japanese Gastric Cancer Association"},{"issue":"5","key":"1749_CR24","first-page":"605","volume":"32","author":"M Cao","year":"2020","unstructured":"Cao M, Li H, Sun D, et al. Classifying risk level of gastric cancer: Evaluation of questionnaire-based prediction model. Chin J cancer Res = Chung-kuo yen cheng yen chiu. 2020;32(5):605\u201313.","journal-title":"Chin J cancer Res = Chung-kuo yen cheng yen chiu"},{"issue":"6","key":"1749_CR25","first-page":"649","volume":"33","author":"R Zhou","year":"2021","unstructured":"Zhou R, Zheng H, Liu M, et al. Development and validation of a questionnaire-based risk scoring system to identify individuals at high risk for gastric cancer in Chinese populations. Chin J cancer Res = Chung-kuo yen cheng yen chiu. 2021;33(6):649\u201358.","journal-title":"Chin J cancer Res = Chung-kuo yen cheng yen chiu"},{"issue":"1","key":"1749_CR26","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1186\/s12916-023-02864-0","volume":"21","author":"X Zhu","year":"2023","unstructured":"Zhu X, Lv J, Zhu M, et al. Development, validation, and evaluation of a risk assessment tool for personalized screening of gastric cancer in Chinese populations. BMC Med. 2023;21(1):159.","journal-title":"BMC Med"},{"issue":"10","key":"1749_CR27","doi-asserted-by":"publisher","first-page":"1378","DOI":"10.1016\/S1470-2045(20)30460-5","volume":"21","author":"G Jin","year":"2020","unstructured":"Jin G, Lv J, Yang M, et al. Genetic risk, incident gastric cancer, and healthy lifestyle: a meta-analysis of genome-wide association studies and prospective cohort study. Lancet Oncol. 2020;21(10):1378\u201386.","journal-title":"Lancet Oncol"},{"issue":"2","key":"1749_CR28","doi-asserted-by":"publisher","first-page":"276","DOI":"10.4251\/wjgo.v15.i2.276","volume":"15","author":"XY Wang","year":"2023","unstructured":"Wang XY, Wang LL, Xu L, et al. Evaluation of polygenic risk score for risk prediction of gastric cancer. World J Gastrointest Oncol. 2023;15(2):276\u201385.","journal-title":"World J Gastrointest Oncol"},{"issue":"1","key":"1749_CR29","doi-asserted-by":"publisher","first-page":"25309","DOI":"10.1038\/s41598-024-75912-1","volume":"14","author":"J Li","year":"2024","unstructured":"Li J, Zhao W, Yang J, et al. Proteomic and serological markers for diagnosing cardia gastric cancer and precursor lesions in a Chinese population. Sci Rep. 2024;14(1):25309.","journal-title":"Sci Rep"},{"issue":"9","key":"1749_CR30","doi-asserted-by":"publisher","first-page":"1576","DOI":"10.1136\/gutjnl-2018-317556","volume":"68","author":"Q Cai","year":"2019","unstructured":"Cai Q, Zhu C, Yuan Y, et al. Development and validation of a prediction rule for estimating gastric cancer risk in the Chinese high-risk population: a nationwide multicentre study. Gut. 2019;68(9):1576\u201387.","journal-title":"Gut"},{"issue":"2","key":"1749_CR31","doi-asserted-by":"publisher","first-page":"e00546","DOI":"10.14309\/ctg.0000000000000546","volume":"14","author":"S He","year":"2023","unstructured":"He S, Sun D, Li H, et al. Real-world practice of gastric cancer prevention and screening calls for practical prediction models. Clin Transl Gastroenterol. 2023;14(2):e00546.","journal-title":"Clin Transl Gastroenterol"}],"container-title":["Gastric Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10120-026-01749-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10120-026-01749-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10120-026-01749-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T06:49:01Z","timestamp":1782715741000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10120-026-01749-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,14]]},"references-count":31,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["1749"],"URL":"https:\/\/doi.org\/10.1007\/s10120-026-01749-4","relation":{},"ISSN":["1436-3291","1436-3305"],"issn-type":[{"value":"1436-3291","type":"print"},{"value":"1436-3305","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,14]]},"assertion":[{"value":"22 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 April 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 June 2026","order":5,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Update","order":6,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The original online version of this article was revised to amend the affiliations 1, 7 and 8.","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no conflict of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"The study was approved by the Institutional Review Board of Zhejiang Cancer Hospital (No. IRB-2025-368(IIT)) and the North West Centre for Research Ethics Committee (11\/NW\/0382). All participants provided written informed consent, and the study was conducted in accordance with the Declaration of Helsinki.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}]}}