Characterization of Platelet Function-Related Gene Predicting Survival and Immunotherapy Efficacy in Gastric Cancer.

Abstract

Immunotherapy is widely used to treat various cancers, but patients with gastric cancer (GC), which has a high mortality rate, benefit relatively less from this therapy. Platelets are closely related to GC progression and metastasis. This study aimed to find novel potential biomarkers related to platelet function to predict GC and immunotherapy efficacy. First, based on platelet activation, signaling, and aggregation (abbreviation: function)-related genes (PFRGs), we used the least absolute shrinkage and selection operator (Lasso) regression method to construct a platelet-function-related genes prognostic score (PFRGPS). PRFGPS was verified in three independent external datasets (GSE26901, GSE15459, and GSE84437) for its robustness and strong prediction performance. Our results demonstrate that PRFGPS is an independent prognostic indicator for predicting overall survival in patients with GC. In addition, prognosis, potential pathogenesis mechanisms, and the response to immunotherapy were defined via gene set enrichment analysis, tumor mutational burden, tumor microenvironment, tumor immune dysfunction and exclusion (TIDE), microsatellite instability, and immune checkpoint inhibitors. We found that the high-PRFGPS subgroup had a cancer-friendly immune microenvironment, a high TIDE score, a low tumor mutational burden, and relatively low microsatellite instability. In the immunophenoscore model, the therapeutic effect on anti-PD-1 and anti-CTLA-4 in the high-PRFGPS subgroup was relatively low. In conclusion, PRFGPS could be used as a reference index for GC prognosis to develop more successful immunotherapy strategies.