Prognostic value and immune infiltration of the gasdermin family in lung adenocarcinoma

Abstract

BackgroundThe GSDM family includes six members, GSDMA, GSDMB, GSDMC, GSDMD, GSDME (DFNA5), and PJVK (Pejvakin, DFNB59), which can induce pyroptosis, thereby regulating the tumorigenesis of various cancers. However, the clinical characteristics and role of the GSDM family in LUAD are not well understood.MethodsIn this study, several important bioinformatics databases were used to integrate the analysis of the expression, prognostic value, and immune infiltration of GSDMs in LUAD. These databases include UALCAN, DiseaseMeth, GEPIA, THPA, cBioPortal, TIMER, WebGestalt, STRING database, and Cytoscape.ResultsThe findings from the UALCAN database revealed that the expression of all six GSDMs based on the tumor stage in LUAD was increased (particularly GSDMD). Our IHC results verified it. Additionally, the DiseaseMeth database showed that the methylation levels of GSDMA, GSDMB, GSDMC, and GSDMD were decreased. The expression of six GSDMs was related to shorter overall survival in patients with LUAD, according to the GEPIA database. The cBioPortal database was further used to explore the alteration rate and correlated genes in LUAD. Subsequently, these genes were subjected to functional enrichment and protein-protein interaction network analyses. We identified that the GSDM family regulate several signaling pathways, including immune-associated signaling pathways. According to tumor-infiltrating immune cell analysis from the TIMER database, GSDM family members are associated with the infiltration of important immune cells and their signature markers.ConclusionsGSDM family may be prognostic markers and novel strategies for the treatment of LUAD.

Gasdermins: a dual role in pyroptosis and tumor immunity

“…From this, it can be inferred that curbing IL-33 and GSDMD may impede the progression of obesity-driven HCC ( 69 , 120 , 121 ). Moreover, high expression of GSDMD in lung adenocarcinoma (LUAD) is associated with larger tumors, advanced lymph node tumor stage, and poor prospects ( 70 , 122 ). However, the expression of GSDMD doesn’t show any linkage with survival rates in lung squamous cell carcinoma (LUSC), suggesting the potential of GSDMD as a standalone prognostic indicator for LUAD ( 70 ).…”

“…However, the expression of GSDMD doesn’t show any linkage with survival rates in lung squamous cell carcinoma (LUSC), suggesting the potential of GSDMD as a standalone prognostic indicator for LUAD ( 70 ). Stifling GSDMD scales down the progression of tumor cells by hampering the EGFR/Akt signaling pathway ( 122 ). Interestingly, simvastatin has the potential to activate the NLRP3/caspase-1 cascade, leading to pyroptosis in LUAD cells ( 123 ).…”

Inflammasomes driven inflammation in lung cancer revisited: a short review

“…Interestingly, high-grade adenocarcinomas show higher levels of NLRP3 inflammasome [42]. Also, studies showed that the GSDMD levels were upregulated in lung adenocarcinoma (LUAD) and LUSC when compared to the matched adjacent normal tissues [46,47]. NLRP3, AIM2, and GSDMD are the most inflammasome components studied in lung cancer.…”

Role of gasdermin family proteins in cancers (Review)

“…Peng et al ( 12 ) found that the expression level of GSDMA was upregulated in lung adenocarcinoma, whereas the methylation level of GSDMA was reduced in cancer tissues compared to that in normal tissues, which may account for the abnormal expression in lung adenocarcinoma. Furthermore, the expression of GSDMA is positively correlated with the infiltration of immune cells in the TME, including B cells, CD8 + T cells, CD4 + T cells, macrophages, neutrophils and dendritic cells, suggesting an underlying association between GSDMA and the effect of immunotherapy ( 12 ). A similar trend was observed in ccRCC, in which the expression level of GSDMA was significantly higher and positively associated with the tumor grade, whereas the methylation level of GSDMA decreased.…”