Development of a Prognostic Model Based on Pyroptosis-Related Genes in Pancreatic Adenocarcinoma

Abstract

Background. The importance of pyroptosis in tumorigenesis and cancer progression is becoming increasingly apparent. However, the efficacy of using pyroptosis-related genes (PRGs) in predicting the prognosis of pancreatic adenocarcinoma (PAAD) patients is unknown. Methods. This investigation used two databases to obtain expression data for PAAD patients. Differentially expressed PRGs (DEPRGs) were identified between PAAD and control samples. Several bioinformatic approaches were used to analyze the biological functions of DEPRGs and to identify prognostic DERPGs. A miRNA-prognostic DEPRG-transcription factor (TF) regulatory network was created via the miRNet online tool. A risk score model was created after each patient’s risk score was calculated. The microenvironments of the low- and high-risk groups were assessed using xCell, the expression of immune checkpoints was determined, and gene set variation analysis (GSVA) was performed. Finally, the efficacy of certain potential drugs was predicted using the pRRophetic algorithm, and the results in the high- and low-risk groups were compared. Results. A total of 13 DEPRGs were identified between PAAD and control samples. Functional enrichment analysis showed that the DEPRGs had a close relationship with inflammation. In univariate and multivariate Cox regression analyses, GSDMC, IRF1, and PLCG1 were identified as prognostic biomarkers in PAAD. The results of the miRNA-prognostic DEPRG-TF regulatory network showed that GSDMC, IRF1, and PLCG1 were regulated by both specific and common miRNAs and TFs. Based on the risk score and other independent prognostic indicators, a nomogram with a good ability to predict the survival of PAAD patients was developed. By evaluating the tumor microenvironment, we observed that the immune and metabolic microenvironments of the two groups were substantially different. In addition, individuals in the low-risk group were more susceptible to axitinib and camptothecin, whereas lapatinib might be preferred for patients in the high-risk group. Conclusion. Our study revealed the prognostic value of PRGs in PAAD and created a reliable model for predicting the prognosis of PAAD patients. Our findings will benefit the prognostication and treatment of PAAD patients.

Exosome and lipid metabolism-related genes in pancreatic adenocarcinoma: a prognosis analysis

“…Furthermore, Su et al reported the high prognostic performance of pyroptosis-related genes ( GSDMC , IRF1 , and PLCG1 ). They found that this model performed well in predicting the 1-, 3- and 5-year survival of TCGA-PAAD patients [ 43 ]. Despite this, our model demonstrates good predictive value in general, and we are the first to examine EALMRG signatures in PAAD prognosis prediction.…”

Gasdermins: a dual role in pyroptosis and tumor immunity

“…Its role in tumor immunity varies depending on the organ and tissue context ( 63 ). Initially, abnormal up-regulation of GSDMC is identified in metastatic melanoma, earning it the label of melanoma-derived leucine zipper extra-nuclear factor (MLZE) and making it a molecular beacon for tracking melanoma evolution ( 27 , 65 ).…”

“…Moreover, GSDMC undergoes hypomethylation in LUAD cells, and elevated levels usually hint at a grim prognosis for LUAD patients ( 63 ). In pancreatic cancer, GSDMC’s presence is nearly double compared to healthy tissues, correlating with reduced patient longevity ( 65 , 129 ). Research led by Yun-Qian Cui indicates pronounced expression of GSDMC in ccRCC, linking it to adverse survival rates ( 54 ).…”

Inflammasome and pyroptosis in autoimmune liver diseases

“…GSDMC can be used as an additional predictive factor for hepatocellular carcinoma ( 64 ). Furthermore, the expression levels of mouse GSDMC are positively correlated with the metastatic ability of B16 melanoma cell lines ( 65 ). However, knockdown of GSMDC attenuates the proliferation of colorectal cancer cell lines ( 66 ).…”