Targeting tumor differentiation grade-related genes prognostic signature including COL5A1 based on single-cell RNA-seq in gastric cancer

Abstract

Background Tumor differentiation grade has been shown to be an independent prognostic factor in gastric cancer (GC). Here,we report a novel tumor differentiation grade-related genes signature to predict prognosis and provide new biomarkers in GC. Methods ScRNA-seq profiles of GC were analyzed by seurat package. Core modules and key genes related to tumor differentiation grade were identified through a weighted gene co-expression network analysis (WGCNA) from The Cancer Genome Atlas (TCGA) database. A prognostic signature associated with tumor differentiation grade module including COL5A1 was constructed in GC and validated. Results We identified the single-cell expression profiling and revealed the cell differentiation, cell clusters, marker genes in GC. Functional enrichment analysis revealed that common differentially expressed genes (DEGs) from cell transition trajectory were mainly enriched in neutrophil process. Integrating clinical factors in GC, WGCNA analysis indicated that tumor differentiation grade module was the most significant. We established and validated this signature based on ten tumor differentiation grade-related genes (TNFAIP2, MAGEA3, CXCR4, COL1A1, FN1, VCAN, PXDN, COL5A1, MUC13 and RGS2). Cox regression analysis showed that age, TNM stage and the risk score were significantly associated with prognosis. And then, these genes could predict prognosis in GC. Finally, the hub gene COL5A1 was a prognostic factor, and obviously correlated with B cells memory, dendritic cells activated, macrophages M0, macrophages M2, plasma cells, T cells follicular helper in GC. Conclusions This study reveals a novel tumor differentiation grade-related genes signature predicting prognosis in GC, and COL5A1 represents a promising biomarker for GC immunotherapy.