Novel Pyroptosis-Related Gene Signatures Identified as the Prognostic Biomarkers for Bladder Carcinoma

Frontiers in Oncology

Xi Yang¹  Yaqin Zhao¹  Yuanfeng Wei¹  Cheng Yi¹  Jia You²  Huawei Li²  Qing Guo³  Peng Fan⁴ 

[1] Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China;Department of Oncology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China;Department of Oncology, Taizhou People’s Hospital, Taizhou, China;Department of Respiratory and Critical Care Medicine, Chongqing Traditional Chinese Medicine Hospital, Chongqing, China;

关键词: bladder carcinoma;    pyroptosis;    prognostic biomarkers;    immune infiltration;    Lasso-Cox regression;   

DOI  :  10.3389/fonc.2022.881860

来源: DOAJ

【 摘 要 】

BackgroundBladder carcinoma (BLCA) is a common malignant tumor with high morbidity and mortality in the urinary system. Pyroptosis is a pattern of programmed cell death that is closely associated with progression of tumors. Therefore, it is significant to probe the expression of pyroptosis-related genes (PRGs) in BLCA.MethodsThe differentially expressed genes in normal and BLCA tissues were first obtained from the Cancer Genome Atlas (TCGA) database analysis, as well as PRGs from the National Center for Biotechnology Information (NCBI) database, intersecting to obtain differentially expressed pyroptosis-related genes (DEPRGs) in BLCA. With the construction of a prognostic model of pyroptosis by regression analysis, we derived and validated key genes, which were ascertained as a separate prognostic marker by individual prognostic and clinical relevance analysis. In addition, we gained six immune cells from the Tumor Immune Evaluation Resource (TIMER) website and analyzed the relationship between pyroptosis prognostic genes and immune infiltration.ResultOur results revealed that 31 DEPRGs were available by comparing normal and BLCA tissues with |log2 (fold change, FC)| > 0.5 and FDR <0.05. Four key genes (CRTAC1, GSDMB, AIM2, and FOXO3) derived from the pyroptosis prognostic model were experimentally validated for consistent expression in BLCA patients. Following risk scoring, the low-risk group of BLCA patients had noticeably higher overall survival (OS) than the high-risk group (p < 0.001). Risk score was still an independent prognostic factor (HR = 1.728, 95% CI =1.289–2.315, p < 0.001). In addition, we found remarkable correlations among the expression of pyroptosis-related prognostic genes and the immune infiltration of CD4+ T cells, CD8+ T cells, B cells, dendritic cells, macrophages, and neutrophils.ConclusionGenes (CRTAC1, GSDMB, AIM2, and FOXO3) associated with pyroptosis are potential BLCA prognostic biomarkers that act as an essential part in the predictive prognosis of survival and immunotherapy of BLCA.

【 授权许可】

Unknown