The Pyroptosis-Related Gene Prognostic Index Associated with Tumor Immune Infiltration for Pancreatic Cancer

Abstract

Pancreatic cancer (PC) is one of the most fatal malignancies. Pyroptosis, a type of inflammatory cell death, likely plays a critical role in the development and progression of tumors. However, the relationship between pyroptosis-related genes (PRGs) and prognosis and immunity to PC is not entirely clear. This study, aimed at identifying the key PRGs in PC, highlights their prognostic value, immune characteristics, and candidate drugs for therapies. We screened 47 differentially expressed PRGs between PC and normal pancreas tissues from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) datasets. Afterwards, a pyroptosis-related gene prognostic index (PRGPI) was constructed based on eight PRGs (AIM2, GBP1, HMGB1, IL18, IRF6, NEK7, NLRP1 and PLCG1) selected by univariate and multivariate Cox regression analysis and LASSO regression analysis, and verified in two external datasets from the International Cancer Genome Consortium (ICGC) and Gene Expression Omnibus (GEO) databases. We found that the PC patients in the PRGPI-defined subgroups not only reflected significantly different levels of infiltration in a variety of immune cells, such as M1 macrophages, but also showed differential expression in genes of the human leukocyte antigen (HLA) family and immune checkpoints. Additionally, molecular characteristics and drug sensitivity also stayed close to the PRGPI risk scores. Therefore, PRGPI may serve as a valuable prognostic biomarker and may potentially provide guidance toward novel therapeutic options for PC patients.

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

“…Conversely, diminished levels of NLRP1 increased the sensitivity of pancreatic cancer cells to ERK inhibitors [46]. Multi-omics analyses further reinforce the prospect of NLRP1 serving as a biomarker for drug sensitivity in pancreatic adenocarcinoma [51,52] and head and neck squamous cell carcinoma [48]. Our comprehensive pharmacogenomic assessment revealed a signi cant correlation between reduced expression of the NLRP1 gene in cancer patients and enhanced sensitivity to a spectrum of chemotherapeutic and targeted agents.…”

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.…”

Significance of pyroptosis-related gene in the diagnosis and classification of rheumatoid arthritis

“…PLCG1, also called phospholipase C, gamma 1, is involved in the receptor tyrosine kinase-(RTK-)-mediated signal transduction pathway ( 47 ). A study found that PRGPI might serve as a prognostic biomarker for pancreatic cancer patients ( 48 ). Besides, numerous studies have proven the involvement of PLCG1-mediated inflammatory response in the pathogenesis of osteoarthritis and lung cancer ( 49 , 50 ).…”