Exploring the Potential of Pyroptosis-Related Genes in Predicting Prognosis and Immunological Characteristics of Pancreatic Cancer From the Perspective of Genome and Transcriptome

Abstract

ObjectiveTo probe into the role of pyroptosis-related genes in pancreatic carcinoma.MethodsHerein, we conducted a comprehensive bioinformatics analysis to evaluate tumor-immune infiltration and tumor mutation burden, the correlations between PRGs, and microsatellite instability and found that 33 PRGS were up- or down-regulated in PC. Then we built the PPI network, which was downloaded from the STRING database. Using TCGA cohort median risk score, PC subjects from the Gene Expression Composite cohort (GEO) data resource were stratified into two risk categories, with the low-PC risk group harboring a higher overall survival (OS) (P = 0.011). We employed the ssGSEA approach to quantify immune cell abundance in separate risk groups separated by risk signature while assessing variations in immune cell invasion. Chemotherapeutic drugs were retrieved from the Genomics of Drug Sensitivity in Cancer (GDSC) data resource.ResultsEight prognostic PRG models (CASP4, GSDMC, IL-18, NLRP1, NLRP2, PLCG1, TIRAP, and TNF) were established via LASSO Cox regression to estimate the OS of PC subjects with medium-to-high accuracy.ConclusionOur study is the first to identify a pyroptotic-related prognostic gene feature for PC, providing more options for the prognostic prediction of PC.

Genome, Metabolism, or Immunity: Which Is the Primary Decider of Pancreatic Cancer Fate through Non-Apoptotic Cell Death?

“…As described by Li et al, this study revealed that NLRP1, NLRP2, IL18, and CASP4 overexpression may contribute to a lower overall survival rate in pancreatic cancer. In this study, TNF was also underexpressed in pancreatic cancer cells [77]. Another study employing almost different PRGs in developing the risk model revealed that the high-risk group decreased anti-tumor immunity by impairing CD8 T and NK cell infiltration in the TME of pancreatic cancer.…”

“…Functional enrichment analysis of PRGs revealed that PRGs were mainly involved in pyroptosis, apoptosis, and other immune signaling pathways (TNF, TLR, and inflammatory response), indicating a conversation among the genome, signaling pathways, and the immune system to connect apoptotic cell death with pyroptosis [77].…”

The NLRP1 inflammasome emerges as a promising therapeutic target and prognostic biomarker across multiple cancer types: A comprehensive pan-cancer analysis

“…Furthermore, the downregulation of NLRP1 is correlated with unfavorable DFS in CHOL. Several studies have explored the potential of NLRP1 as a prognostic biomarker in various cancers, including lung adenocarcinoma [39,40,44], gastric cancer [45], prostate cancer [43], pancreatic cancer [46,47], head and neck squamous cell carcinoma [48], and laryngeal carcinoma [49]. Shen et al con rmed that decreased expression of NLRP1 was signi cantly associated with a poor prognosis of LUAD [41].…”

Construction and comprehensive analysis of a novel prognostic signature associated with pyroptosis molecular subtypes in patients with pancreatic adenocarcinoma

“…Similar to these studies, our study also carried out methods such as survival analysis, ROC and external cohort validation of PMSRPS, but it still has its advantages. First, after knowing the importance of subtyping based on molecular characteristics of cancer for improving clinical treatment decision-making, we did not directly use PRGs to establish a prognostic signature as many previous studies had done (84)(85)(86)(87)(88), but instead identified three stable pyroptosis molecular subtypes based on PRGs expression levels. By analysis, we found that different PRGclusters had different survival outcomes and immune cell infiltration manifestations.…”