Microsatellite instability in gastric cancer: molecular features and clinical implications

Abstract

Gastric cancer (GC), a molecularly and phenotypically highly heterogeneous malignancy, is a leading cause of cancer-related deaths. The Cancer Genome Atlas (TCGA) project identifies the microsatellite instability (MSI) subtype of GC, which has garnered increasing attention due to its relatively favorable survival outcome and better response to immune checkpoint inhibitors (ICIs). The occurrence of MSI is closely associated with the defects in mismatch repair system, subsequently leading to the accumulation of mutations in cell genome, particularly in microsatellites. Based on the exclusive features of MSI GC, several detection methods like immunohistology have been developed to determine MSI status clinically, with novel detection methods developing. It is clinically observed that MSI GC tends to have a better response to ICIs treatment while its response to chemotherapy is controversial, necessitating further investigation into the underlying mechanisms. In this review, we systemically summarized the molecular features, detection method, clinico-pathological characteristics and prognosis of MSI GC, offering a comprehensive overview of this unique GC subtype.