You Jia, Li Huawei, Wei Yuanfeng, Fan Peng, Zhao Yaqin, Yi Cheng, Guo Qing, Yang Xi
Department of Oncology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Front Oncol. 2022 Jun 30;12:881860. doi: 10.3389/fonc.2022.881860. eCollection 2022.
Bladder 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.
The 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.
Our 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 ( < 0.001). Risk score was still an independent prognostic factor (HR = 1.728, 95% CI =1.289-2.315, < 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.
Genes (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.
膀胱癌（BLCA）是泌尿系统中一种常见的恶性肿瘤，发病率和死亡率较高。细胞焦亡是一种程序性细胞死亡模式，与肿瘤进展密切相关。因此，探究细胞焦亡相关基因（PRGs）在膀胱癌中的表达具有重要意义。
首先从癌症基因组图谱（TCGA）数据库分析中获取正常组织和膀胱癌组织中的差异表达基因，以及来自美国国立生物技术信息中心（NCBI）数据库的PRGs，通过交集获得膀胱癌中差异表达的细胞焦亡相关基因（DEPRGs）。通过回归分析构建细胞焦亡预后模型，推导并验证关键基因，通过个体预后和临床相关性分析将其确定为独立的预后标志物。此外，我们从肿瘤免疫评估资源（TIMER）网站获得六种免疫细胞，并分析细胞焦亡预后基因与免疫浸润之间的关系。
我们的结果显示，通过比较正常组织和膀胱癌组织，|log2（倍数变化，FC）|>0.5且FDR<0.05，可获得31个DEPRGs。从细胞焦亡预后模型中推导的四个关键基因（CRTAC1、GSDMB、AIM2和FOXO3）在膀胱癌患者中的表达一致性得到实验验证。经过风险评分，膀胱癌低风险组患者的总生存期（OS）明显高于高风险组（<0.001）。风险评分仍是独立的预后因素（HR=1.728，95%CI=1.289-2.315，<0.001）。此外，我们发现细胞焦亡相关预后基因的表达与CD4 T细胞、CD8 T细胞、B细胞、树突状细胞、巨噬细胞和中性粒细胞的免疫浸润之间存在显著相关性。
与细胞焦亡相关的基因（CRTAC1、GSDMB、AIM2和FOXO3）是潜在的膀胱癌预后生物标志物，在膀胱癌生存预测预后和免疫治疗中起重要作用。
