Liang Chaowei, Fan Jiaxin, Liang Chaojie, Guo Jiansheng
Department of Gastrointestinal Surgery, First Hospital of Shanxi Medical University, Taiyuan, China.
Department of Hepatobiliary and Pancreatic Surgery, First Hospital of Shanxi Medical University, Taiyuan, China.
Front Genet. 2022 Feb 25;12:699503. doi: 10.3389/fgene.2021.699503. eCollection 2021.
Pyroptosis is an inflammatory form of programmed cell death triggered by caspase-1/4/5/11 that plays an important role in the occurrence and development of gastric cancer (GC). We investigated the prognostic value of pyroptosis-related genes in GC. The "LIMMA" R package and univariate Cox analysis were used to find pyroptosis-related genes with differential expression and prognostic value in the TCGA cohort and the identified genes were analyzed for GO enrichment and KEGG pathways. The selected genes were then included in a multivariate Cox proportional hazard regression analysis, and a ten genes prognostic model (BIRC2, CD274, IRGM, ANXA2, GBP5, TXNIP, POP1, GBP1, DHX9, and TLR2) was established. To evaluate the predictive value of the risk score on prognosis, patients were divided into high-risk and low-risk groups according to the median risk score, and survival analysis was carried out. Compared with the low-risk group, the OS of GC patients in the high-risk group was significantly worse. Additionally, these results were verified in the GSE84437 and GSE66229 datasets. Finally, through the combination of prognostic gene characteristics and clinicopathological features, a nomogram was established to predict individual survival probability. The results show that the genetic risk characteristics related to clinical features can be used as independent prognostic indicators for patients with GC. In summary, the pyroptosis-related risk signals proposed in this study can potentially predict the prognosis of patients with GC. In addition, we also found significant infiltration of dendritic cells, macrophages, and neutrophils in tissues of high-risk patients.
细胞焦亡是一种由半胱天冬酶-1/4/5/11触发的程序性细胞死亡的炎症形式，在胃癌（GC）的发生和发展中起重要作用。我们研究了细胞焦亡相关基因在GC中的预后价值。使用“LIMMA”R包和单变量Cox分析在TCGA队列中寻找具有差异表达和预后价值的细胞焦亡相关基因，并对鉴定出的基因进行GO富集和KEGG通路分析。然后将所选基因纳入多变量Cox比例风险回归分析，并建立了一个包含十个基因的预后模型（BIRC2、CD274、IRGM、ANXA2、GBP5、TXNIP、POP1、GBP1、DHX9和TLR2）。为了评估风险评分对预后的预测价值，根据中位风险评分将患者分为高风险组和低风险组，并进行生存分析。与低风险组相比，高风险组GC患者的总生存期明显更差。此外，这些结果在GSE84437和GSE66229数据集中得到了验证。最后，通过结合预后基因特征和临床病理特征，建立了一个列线图来预测个体生存概率。结果表明，与临床特征相关的遗传风险特征可作为GC患者的独立预后指标。总之，本研究提出的细胞焦亡相关风险信号有可能预测GC患者的预后。此外，我们还发现高风险患者组织中树突状细胞、巨噬细胞和中性粒细胞有明显浸润。
