Abstract

BACKGROUND: Specific features of the tumor microenvironment (TME) may provide useful prognostic information. We conducted a systematic investigation of the cellular composition and prognostic landscape of TME in gastric cancer.METHODS: We evaluated the prognostic significance of major stromal and immune cells within TME. We proposed a composite TME-based risk score and tested it in six independent cohorts of 1,678 patients with gene expression or immunohistochemistry measurements. Further, we devised a new patient classification system based on TME characteristics.RESULTS: We identified natural killer cells, fibroblasts, and endothelial cells as the most robust prognostic markers. The TME risk score combining these cell types was an independent prognostic factor when adjusted for clinicopathologic variables (gene expression: HR [95% CI]: 1.42 [1.22-1.66]; immunohistochemistry: 1.34 [1.24-1.45], P<0.0001). Higher TME risk scores consistently associated with worse survival within every pathologic stage (HR range: 2.18-3.11, P<0.02) and among patients who received surgery only. The TME risk score provided additional prognostic value beyond stage, and combination of the two improved prognostication accuracy (likelihood-ratio test chi2 = 235.4 vs. 187.6, P<0.0001; net reclassification index: 23%). The TME risk score can predict the survival benefit of adjuvant chemotherapy in non-metastatic patients (stage I-III) (interaction test P<0.02). Patients were divided into four TME subtypes that demonstrated distinct genetic and molecular patterns and complemented established genomic and molecular subtypes.CONCLUSION: We developed and validated a TME-based risk score as an independent prognostic and predictive factor, which has the potential to guide personalized management of gastric cancer.

View details for DOI 10.1172/jci.insight.136570

View details for PubMedID 32229725