Molecular characteristics, clinical significance and cancer‑immune interactions of pyroptosis‑related genes in colorectal cancer.

Abstract

Colorectal cancer (CRC) is a malignant tumor with poor prognosis. Pyroptosis is a newly discovered type of programmed cell death that is typically accompanied by a strong inflammatory response. Accumulating evidence suggests that pyroptosis-related genes (PRGs) may have important roles in the development of malignant tumors. However, the association between PRG expression and clinical outcomes in CRC remain unclear. In the present study, the genetic variations and transcriptional patterns of 52 PRGs were comprehensively analyzed using cohorts from The Cancer Genome Atlas and Gene Expression Omnibus and the mRNA expression levels of 7 PRGs in collected CRC samples were validated using reverse transcription-quantitative PCR. Using LASSO-Cox analysis, a PRG score was then generated and the relationship between the PRG score and prognosis, immune cell infiltration and drug sensitivity in CRC was uncovered. In the present study, the mutation and expression patterns of PRGs were analyzed and it was found that these genes were differentially expressed in CRC tissues compared with normal tissues. Based on the expression patterns of the PRGs, patients with CRC were divided into two subtypes (cluster A and B), of which cluster B had an improved prognosis and a higher abundance of immune cells. Next, differentially expressed genes between clusters A and B were identified and a PRG risk score closely related to the prognosis of CRC was constructed. Then, a nomogram for evaluating the overall survival of patients was constructed. Furthermore, a low PRG risk score was characterized by immune activation and closely related to the microsatellite instability-high pattern. Additionally, the PRG risk score was notably correlated with drug sensitivity. In conclusion, the mutation and expression characteristics of PRGs in CRC were comprehensively analyzed and a prognostic PRG signature was constructed in the present study. This signature may predict immune cell infiltration and therapeutic response in CRC, providing new insights into the prognosis and treatment of CRC.