RSAD2, a pyroptosis-related gene, predicts the prognosis and immunotherapy response for colorectal cancer

Abstract

Abstract BACKGROUND Colorectal cancer (CRC) is one of the most common malignant tumors and exhibits high levels of heterogeneity. Although many treatments and medications are available, the long-term survival rate of CRC patients is far from satisfactory. OBJECTIVE Pyroptosis is closely related to tumor progression, and we aimed to identify pyroptosis-related genes (PRGs) and candidate biomarkers to predict the prognosis of CRC patients. METHODS The expression profiles from Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database were used to identify cancer hallmarks associated with CRC outcomes. WGCNA was performed to explore differential expression genes (DEGs). The STRING database and Cytoscape were used to construct a protein-protein interaction (PPI) network and identify the hub genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) were used to access the functional pathway related to hub genes. Real-Time Quantitative Revers Transcription PCR (RT-qPCR) was chosen to validate the expression of RSAD2 in CRC patients and its effect on pyroptosis. RESULTS 288 co-expression genes in CRC between pyroptosis-related modules and DEGs were identified. Among these hub genes, we selected the top 24 for further analysis and found that RSAD2 was a novel biomarker associated with the progression of CRC. In addition, RSAD2 also affected the tumor immune microenvironment and prognostic of CRC. A risk model for RSAD2 was identified as an independent prognostic predictor. The receiver operator characteristic analysis showed that the model had an acceptable prognostic value for patients with CRC. In addition, RSAD2 also affects the tumor immune microenvironment and prognosis of CRC. We further validated RSAD2 expression in CRC patients and the model using qPCR and the role of RSAD2 in pyroptosis. CONCLUSIONS The comprehensive analysis of pyroptosis-related genes (PRGs) in CRC demonstrated their potential in the tumor-immune microenvironment, clinic-pathological features, and prognosis. Furthermore, this study comprehensively assessed the expression and prognosis of RSAD2 in CRC patients. These findings may offer a new direction for early CRC screening and development of future immunotherapy strategies.