PeerJ (Oct 2024)
In-depth study of pyroptosis-related genes and immune infiltration in colon cancer
Abstract
Background Pyroptosis is a form of regulated necrosis that occurs in many cell and tissue types and plays a critical role in tumor progression. The diagnostic value of pyroptosis-related genes (PRGs) in colon cancer has been widely investigated. In the present study, we explored the relationship between PRG expression and colon cancer. Methods We retrieved genomic and clinical data pertaining to The Cancer Genome Atlas-Colon Adenocarcinoma from the UCSC Xena database, along with the corresponding genome annotation information from the GENCODE data portal. Utilising these data and a list of 33 pyrogenic genes, we performed principal component analysis and unsupervised clustering analysis to assess the pyroptosis subtypes. We analysed the differential expression between these subtypes to obtain PRGs, ultimately selecting 10 PRGs. We conducted Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, gene set variation analysis, protein–protein interaction, and immune infiltration analyses of these PRGs. We validated the expression of TNNC1 via immunohistochemistry (IHC) and real-time quantitative PCR. Results After rigorous screening, excluding patients with incomplete survival data and unmatched transcriptomes, we refined our study cohort to 431 patients. We performed differential mRNA analysis and identified 445 PRGs, 10 of which were selected as hub genes. These genes were associated with various immune cell types. Specifically, TNNC1 expression was positively associated with immature dendritic cells and NK CD56+ cells. IHC staining indicated higher TNNC1 expression levels in tumor samples. Notably, TNNC1 expression levels were high in all the colon cancer cell lines, particularly in SW480 cells. Conclusion In this study, we explored the characteristics of PRGs in colon cancer and identified novel biological targets for early individualised treatment and accurate diagnosis of colon cancer, thus contributing to the advancement of clinical oncology.
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