Identification of collagen subtypes of gastric cancer for distinguishing patient prognosis and therapeutic response

BACKGROUND: Gastric cancer is a highly heterogeneous disease, presenting a major obstacle to personalized treatment. Effective markers of the immune checkpoint blockade response are needed for precise patient classification. We, therefore, divided patients with gastric cancer according to collagen gene expression to indicate their prognosis and treatment response. METHODS: We collected data for 1250 patients with gastric cancer from four cohorts. For the TCGA-STAD cohort, we used consensus clustering to stratify patients based on expression levels of 44 collagen genes and compared the prognosis and clinical characteristics between collagen subtypes. We then identified distinct transcriptomic and genetic alteration signatures for the subtypes. We analyzed the associations of collagen subtypes with the responses to chemotherapy, immunotherapy, and targeted therapy. We also established a platform-independent collagen-subtype predictor. We verified the findings in three validation cohorts (GSE84433, GSE62254, and GSE15459) and compared the collagen subtyping method with other molecular subtyping methods. RESULTS: We identified two subtypes of gastric adenocarcinoma: a high-expression collagen subtype (CS-H) and a low-expression collagen subtype (CS-L). Collagen subtype was an independent prognostic factor, with better overall survival in the CS-L subgroup. The inflammatory response, angiogenesis, and phosphoinositide 3-kinase (PI3K)/Akt pathways were transcriptionally active in...