Constructing and Validating a Pyroptosis-Related Genes Prognostic Signature for Stomach Adenocarcinoma and Immune Infiltration: Potential Biomarkers for Predicting the Overall Survival

Abstract

Background. Stomach adenocarcinoma (STAD) is a kind of cancer that begins in the stomach cells and has a poor overall survival rate. Following resection surgery, chemotherapy has been suggested as a curative method for stomach cancer. However, it is ineffective. Pyroptosis, a kind of inflammatory programmed cell death, has been shown to play a significant role in the development and progression of STAD. However, whether pyroptosis-related genes (PRGs) can be utilized to predict the diagnosis and prognosis of gastric cancer remains unknown. Method. The research measured at predictive PRGs in STAD samples from TCGA and GEO. Lasso regression was used to build the prediction model. Coexpression analysis revealed that gene expression was linked to pyroptosis. PRGs were found to be overexpressed in high-risk individuals, implying that they could be used in a model to predict STAD prognosis. Result. Immunological and tumor-related pathways were discovered using GSEA. In STAD patients, the genes GPX3, PDGFRL, RGS2, and SERPINE1 may be connected to the cancer process. The levels of expression also differed between the two risk groups. Conclusion. The purpose of this study is to identify and verify STAD-associated PRGs that can effectively guide prognosis and the immunological milieu in STAD patients as well as offer evidence for the development of pyroptosis-related molecularly targeted therapeutics. Therefore, PRGs and the link between immunological and PRGs in STAD may be therapeutic targets.

M6A methylation of FKFB3 reduced pyroptosis of gastric cancer by NLRP3

“…IL-1β induces cell death by forming pores in the cell membrane through caspase-1, 4, 5 and 11. The NLRP3 inflammasome has been identified as a key component in the initiation of pyroptosis [39,40]. Our findings demonstrate that the upregulation of PFKFB3 reduces pyroptosis in GC cells.…”

“…Research has found that when cells are stimulated by pathogenic and damage-related molecular patterns, inflammatory caspase-1 activation is induced, leading to the shear formation of GSDMD-C and cytotoxic GSDMD-N, the executors of cell pyroptosis. The latter is recruited to form cell pyroptosis pores, promoting the maturation of IL-1 β release of IL-18 into the extracellular space, inducing an inflammatory cascade reaction [39,40]. Pyroptosis is initiated by endogenous danger signals or metabolites, leading to the production of IL-1β.…”

Comprehensive multi-omics analysis of pyroptosis for optimizing neoadjuvant immunotherapy in patients with gastric cancer

“…In addition, RGS1 , another component of the PRS calculation, was found to be a novel marker of CD8 + T cell depletion, leading to sustained antigenic stimulation and T-cell depletion, according to single-cell transcriptome analysis by Bai et al 36 . RGS is also a member of the pyroptosis-related gene model proposed by Xu et al , thereby implying its pivotal role in the process of pyroptosis 37 . Additionally, we observed that the association between the PRS and macrophage polarization was limited to the tumor center, possibly because of the presence of VCAN , a constituent molecule of the PRS.…”

Progress and perspectives of cellular pyroptosis in digestive tract tumors

“…Most importantly, the high expression of LncRNA ADAMTS9-AS2 also sensitizes gastric cancer cells that originally showed resistance to cisplatin [32] . Studies have shown that overexpression of lncRNA ADAMTS9-AS2 inhibits gastric cancer development by regulating the miR-223-3p/NLRP3 axis-mediated pyroptosis process [33,34] . In addition, Icariin (ICA), which is mainly found in Epimedium, has multiple biological activities, and the anticancer effects of ICA are associated with the signaling axis between hsa_circ_0003159, miR-223-3p, and NLRP3.…”