{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T05:05:08Z","timestamp":1789621508406,"version":"build-2803163510"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aimed to systematically assess the predictive value of microsatellite instability (MSI) combined with programmed death-ligand 1 (PD-L1) expression for prognosis and immunotherapy response in patients with gastric cancer (GC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      An individual patient data (IPD) meta-analysis was performed in accordance with the PICOS framework and PRISMA 2020 guidelines. A comprehensive literature search was performed across English and Chinese databases to identify cohort studies or randomized controlled trials (RCTs) that simultaneously evaluated MSI status and PD-L1 expression, and reported overall survival (OS), disease-free survival (DFS) with 95% confidence intervals (CIs) were used as pooled effect measures. Fixed-effect or random-effects models were applied based on heterogeneity assessed by the\n                      <jats:italic>I<\/jats:italic>\n                      \u00b2 statistic. Subgroup analyses were stratified by ethnicity, pathological stage, Lauren classification, chemotherapy timing, MSI detection platform, and PD-L1 antibody clone. The interactive effect of MSI-H and PD-L1 expression was evaluated using radar plots.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Nine studies involving 6,667 GC patients were included. For OS, MSI-H alone (HR\u00a0=\u00a00.500, 95%CI: 0.357-0.700,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.001), and MSI-H\/MSI-L combined (HR\u00a0=\u00a00.641, 95%CI: 0.437-0.939,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.025) were associated with better outcomes than MSS; PD-L1 positivity predicted poorer OS (HR\u00a0=\u00a01.517, 95%CI: 1.077-2.137,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.017); MSI-H+PD-L1 negative patients had the most favorable OS (HR\u00a0=\u00a00.380, 95%CI: 0.255-0.566,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.001), while MSI-H+PD-L1 positive patients had poorer OS than MSS+PD-L1 negative patients (HR\u00a0=\u00a02.076, 95%CI: 1.238-3.479,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.006). For DFS, MSI-H alone (HR\u00a0=\u00a00.506, 95%CI: 0.360-0.710,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.001) and MSI-H\/MSI-L combined (HR\u00a0=\u00a00.530, 95%CI: 0.402-0.698,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.001) outperformed MSS, but PD-L1 expression showed no significant DFS association (HR\u00a0=\u00a01.189, 95%CI: 0.472-2.998,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.709). Subgroup analyses identified TNM stage, Lauren classification, chemotherapy timing, and MSI detection method as significant effect modifiers (all interaction\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.05). Pooled immunotherapy data showed that MSI-H patients had higher ORR than MSS (OR\u00a0=\u00a03.580,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.001), and MSI-H+PD-L1 positive patients achieved the highest response rates (OR\u00a0=\u00a04.100 vs. MSI-H+PD-L1 negative,\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&amp;lt;\u00a00.001). Sensitivity analysis confirmed result stability, and publication bias was minimal.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>MSI-H status is a robust favorable prognostic factor for GC, while PD-L1 positivity indicates adverse OS prognosis. The combination of MSI and PD-L1 expression enables refined prognostic stratification of GC patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1900024","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T04:50:19Z","timestamp":1789620619000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Microsatellite instability combined with PD-L1 expression in prognosis of gastric cancer: an integrated analysis based on individual patient data"],"prefix":"10.3389","volume":"16","author":[{"given":"Yajing","family":"Feng","sequence":"first","affiliation":[{"name":"Department of Nosocomial Infection Management, The First Affiliated Hospital of Zhengzhou University","place":["Zhengzhou, Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengmeng","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Medical Research Office, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital","place":["Zhengzhou, Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhui","family":"Chai","sequence":"additional","affiliation":[{"name":"Department of Medical Research Office, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital","place":["Zhengzhou, Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jicun","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Nosocomial Infection Management, The First Affiliated Hospital of Zhengzhou University","place":["Zhengzhou, Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuehua","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Public Health, Zhengzhou University","place":["Zhengzhou, Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaijuan","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Public Health, Zhengzhou University","place":["Zhengzhou, Henan, China"]},{"name":"Henan Key Laboratory of Tumor Epidemiology, Henan International Joint Laboratory of Tumor Biomarkers and Molecular Imaging, Zhengzhou University","place":["Zhengzhou, Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fujiao","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Medical Research Office, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital","place":["Zhengzhou, Henan, China"]},{"name":"Henan Key Laboratory of Tumor Epidemiology, Henan International Joint Laboratory of Tumor Biomarkers and Molecular Imaging, Zhengzhou University","place":["Zhengzhou, Henan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"394","DOI":"10.3322\/caac.21492","article-title":"Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"68","author":"Bray","year":"2018","journal-title":"CA Cancer J Clin"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1097\/sla.0000000000004303","article-title":"Comprehensive molecular characterization of adenocarcinoma of the gastroesophageal junction between esophageal and gastric adenocarcinomas","volume":"275","author":"Suh","year":"2022","journal-title":"Ann Surg"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.21037\/jgo-21-695","article-title":"Microsatellite instability in Chinese gastric cancer and its correlation with clinical characteristics","volume":"12","author":"Li","year":"2021","journal-title":"J Gastrointest Oncol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.82627","article-title":"Pattern of deficient mismatch repair (dMMR)\/ high microsatellite instability (MSI-H) testing in India: a questionnaire-based study","volume":"17","author":"Pednekar","year":"2025","journal-title":"Cureus"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1500596","article-title":"PD-1 blockade in tumors with mismatch-repair deficiency","volume":"372","author":"Le","year":"2015","journal-title":"N Engl J Med"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1200\/jco.19.01124","article-title":"Individual patient data meta-analysis of the value of microsatellite instability as a biomarker in gastric cancer","volume":"37","author":"Pietrantonio","year":"2019","journal-title":"J Clin Oncol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00910","article-title":"Innate lymphoid cells: expression of PD-1 and other checkpoints in normal and pathological conditions","volume":"10","author":"Mariotti","year":"2019","journal-title":"Front Immunol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/s41416-020-01053-7","article-title":"Immunophenotype based on inflammatory cells, PD-1\/PD-L1 signalling pathway and M2 macrophages predicts survival in gastric cancer","volume":"123","author":"Junttila","year":"2020"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.tranon.2025.102465","article-title":"Isolated tumor cell clusters (ITC) in lymph nodes and PD-L1 expression on tumor-associated immune cells are prognostic factors for microsatellite instable-high gastric cancers","volume":"59","author":"Cui","year":"2025","journal-title":"Transl Oncol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"9344124","DOI":"10.1155\/2021\/9344124","article-title":"Immune score predicts outcomes of gastric cancer patients treated with adjuvant chemoradiotherapy","author":"Zou","year":"2021"},{"key":"B12","article-title":"Immunohistochemical-based molecular typing of ACRG combined with immune-associated PD-L1 expression can predict the prognosis of gastric cancer","volume":"14","author":"Li","year":"2025"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.4143\/crt.2020.173","article-title":"A multi-cohort study of the prognostic significance of microsatellite instability or mismatch repair status after recurrence of resectable gastric cancer","volume":"52","author":"An","year":"2020","journal-title":"Cancer Res Treat"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1634\/theoncologist.2019-0471","article-title":"Prognostic and predictive value of microsatellite instability, inflammatory reaction and PD-L1 in gastric cancer patients treated with either adjuvant 5-FU\/LV or sequential FOLFIRI followed by cisplatin and docetaxel: a translational analysis from the ITACA-S trial","volume":"25","author":"Di Bartolomeo","year":"2020"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3760\/cma.j.cn112151-20200323-00245","article-title":"Expression level and prognostic value of PD-L1 in microsatellite instability-high gastric cancer","volume":"49","author":"Wang","year":"2020","journal-title":"Zhonghua Bing Li Xue Za Zhi"},{"key":"B16","volume-title":"Expression of CD8\/PD-L1 and MSI in Gastric Cancer and its Correlation With Prognosis","author":"Li","year":"2021"},{"key":"B17","article-title":"Study on the relationship between MSI, HGF and clinicopathological characteristics and prognosis of gastric cancer","volume":"13","author":"Meng","year":"2021","journal-title":"J Mol Diagnosis Ther"},{"key":"B18","article-title":"Relationship between programmed death ligand-1 expression and prognosis of gastric cancer patients with microsatellite instability","volume":"36","author":"Wang","year":"2022","journal-title":"J Chin Pract Diagnosis Ther"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1200\/jco.2024.42.16_suppl.4039","article-title":"Perioperative chemotherapy for gastric cancer patients with microsatellite instability or deficient mismatch repair: a systematic review and meta-analysis","volume":"131","author":"Liu","year":"2025"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.26399","article-title":"Microsatellite instability in sporadic gastric cancer: its prognostic role and guidance for 5-FU based chemotherapy after R0 resection","volume":"131","author":"An","year":"2012","journal-title":"Int J Cancer"},{"key":"B21","doi-asserted-by":"publisher","first-page":"699","DOI":"10.3892\/mco.2015.506","article-title":"Microsatellite instability and survival in gastric cancer: a systematic review and meta-analysis","volume":"3","author":"Zhu","year":"2015","journal-title":"Mol Clin Oncol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1002\/bjs.10663","article-title":"Meta-analysis of microsatellite instability in relation to clinicopathological characteristics and overall survival in gastric cancer","volume":"105","author":"Polom","year":"2018"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.808964","article-title":"Tumor-infiltrating lymphocytes in colorectal cancer: the fundamental indication and application on immunotherapy","volume":"12","author":"Bai","year":"2021","journal-title":"Front Immunol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/srep37933","article-title":"The clinicopathological and prognostic significance of PD-L1 expression in gastric cancer: a meta-analysis of 10 studies with 1,901 patients","volume":"6","author":"Zhang","year":"2016","journal-title":"Sci Rep"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.908026","article-title":"A meta-analysis with systematic review: efficacy and safety of immune checkpoint inhibitors in patients with advanced gastric cancer","volume":"12","author":"El Helali","year":"2022","journal-title":"Front Oncol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1136\/gutjnl-2015-310839","article-title":"Patterns of PD-L1 expression and CD8 T cell infiltration in gastric adenocarcinomas and associated immune stroma","volume":"66","author":"Thompson","year":"2017","journal-title":"Gut"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.19318","article-title":"PD-1 and PD-L1 co-expression predicts favorable prognosis in gastric cancer","volume":"8","author":"Wu","year":"2017","journal-title":"Oncotarget"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2018.0013","article-title":"Safety and efficacy of pembrolizumab monotherapy in patients with previously treated advanced gastric and gastroesophageal junction cancer: phase 2 clinical KEYNOTE-059 trial","volume":"4","author":"Fuchs","year":"2018","journal-title":"JAMA Oncol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2024.1382183","article-title":"Progress and prospects of biomarker-based targeted therapy and immune checkpoint inhibitors in advanced gastric cancer","volume":"14","author":"Zeng","year":"2024","journal-title":"Front Oncol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1186\/s12885-026-15880-z","article-title":"Prognostic implications of PD-L1 expression in gastric cancer: systematic review and meta-analysis of studies published between 2018 and 2025","volume":"26","author":"Yessultanova","year":"2026","journal-title":"BMC Cancer"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1007\/s00262-020-02694-6","article-title":"Immunoscore is a strong predictor of survival in the prognosis of stage II\/III gastric cancer patients following 5-FU-based adjuvant chemotherapy","volume":"70","author":"Yun","year":"2021"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1080\/14796694.2024.2342107","article-title":"Zolbetuximab plus chemotherapy for locally advanced unresectable or metastatic stomach or gastroesophageal junction cancers: a plain language summary","volume":"20","author":"Shitara","year":"2024","journal-title":"Future Oncol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"17588359231171038","DOI":"10.1177\/17588359231171038","article-title":"First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric cancer, gastroesophageal junction cancer, and esophageal adenocarcinoma: a cost-effectiveness analysis","volume":"15","author":"Cao","year":"2023"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1900024\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T04:50:31Z","timestamp":1789620631000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2026.1900024\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,17]]},"references-count":33,"alternative-id":["10.3389\/fonc.2026.1900024"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2026.1900024","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,17]]},"article-number":"1900024"}}