Microsatellite instability combined with PD-L1 expression in prognosis of gastric cancer: an integrated analysis based on individual patient data
In brief
MSI-high, PD-L1-positive gastric cancers had 4 times higher immunotherapy response odds
An individual-patient analysis of 9 studies and 6,667 people found that MSI-high tumors had better overall and disease-free survival than microsatellite-stable tumors, while PD-L1 positivity was linked to worse overall survival. Among MSI-high patients receiving immunotherapy, those with PD-L1-positive tumors had 4.1 times the response odds of those with PD-L1-negative tumors; differences across clinical subgroups limit how broadly to apply the findings.
- Journal
- Frontiers in oncology (Q2)
- Published
- 17 September 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Yajing Feng, Mengmeng Yin, Junhui Chai, Jicun Zhu, Yuehua Zhang, Kaijuan Wang, et al.
- PMID
- 42824091
- DOI
- 10.3389/fonc.2026.1900024
Why clinicians should know about it
- Picked for Pathology and Forensic Medicine (top studies of the week, 4 October 2026).
Abstract
OBJECTIVE: 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). METHODS: 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 I² 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. RESULTS: Nine studies involving 6,667 GC patients were included. For OS, MSI-H alone (HR = 0.500, 95%CI: 0.357-0.700, P < 0.001), and MSI-H/MSI-L combined (HR = 0.641, 95%CI: 0.437-0.939, P = 0.025) were associated with better outcomes than MSS; PD-L1 positivity predicted poorer OS (HR = 1.517, 95%CI: 1.077-2.137, P = 0.017); MSI-H+PD-L1 negative patients had the most favorable OS (HR = 0.380, 95%CI: 0.255-0.566, P < 0.001), while MSI-H+PD-L1 positive patients had poorer OS than MSS+PD-L1 negative patients (HR = 2.076, 95%CI: 1.238-3.479, P = 0.006). For DFS, MSI-H alone (HR = 0.506, 95%CI: 0.360-0.710, P < 0.001) and MSI-H/MSI-L combined (HR = 0.530, 95%CI: 0.402-0.698, P < 0.001) outperformed MSS, but PD-L1 expression showed no significant DFS association (HR = 1.189, 95%CI: 0.472-2.998, P = 0.709). Subgroup analyses identified TNM stage, Lauren classification, chemotherapy timing, and MSI detection method as significant effect modifiers (all interaction P < 0.05). Pooled immunotherapy data showed that MSI-H patients had higher ORR than MSS (OR = 3.580, P < 0.001), and MSI-H+PD-L1 positive patients achieved the highest response rates (OR = 4.100 vs. MSI-H+PD-L1 negative, P < 0.001). Sensitivity analysis confirmed result stability, and publication bias was minimal. CONCLUSION: 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.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.