Shi Qi, Liu Meichen, Wang Shuo, Ding Pengpeng, Wang Yuefu
Department of Oncology, Beijing Shijitan Hospital of Capital Medical University, Beijing, China.
Department of Surgery ICU, Beijing Shijitan Hospital of Capital Medical University, Beijing, China.
J Thorac Dis. 2023 Mar 31;15(3):1387-1397. doi: 10.21037/jtd-23-206.
Esophageal squamous cell carcinoma (ESCC) has a poor prognosis, and the 5-year survival rate is less than 30%. Better differentiation of patients at high risk of recurrence or metastasis could guide clinical treatment. The close relationship between pyroptosis and ESCC has been recently reported. Herein, we aimed to identify genes associated with pyroptosis in ESCC and construct a prognostic risk model.
RNA-seq data of ESCC was obtained from the The Cancer Genome Atlas (TCGA) database. Gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA) were used to calculate the pyroptosis-related pathway score (Pys). Weighted gene co-expression network analysis (WGCNA) and univariate Cox regression were used to screen for pyroptotic genes associated with prognosis, and Lasso regression was used to establish a risk score. Finally, the T test was used to compare the relationship between the model and tumor-node-metastasis (TNM) stage. Furthermore, we compared the difference of immune infiltrating cells and immune checkpoints between the low- and high-risk groups.
Using WGCNA, 283 genes were significantly associated with N staging and Pys. Among them, univariate Cox analysis suggested that 83 genes were associated with prognosis of ESCC patients. After that, , , and were identified as prognostic signatures separating high- and low-risk groups. Patients in the high- and low-risk groups had significantly different distributions of T (P=0.018) and N staging (P<0.05). Moreover, the 2 groups had remarkably different immune infiltrating cell scores and immune checkpoint expressions.
Our study identified 3 prognosis pyroptosis-related genes in the ESCC and successfully build a prognostic model. , , and 3 may serve as promising therapeutic targets in ESCC.
食管鳞状细胞癌（ESCC）预后较差，5年生存率低于30%。更好地鉴别复发或转移高危患者可指导临床治疗。最近有报道称细胞焦亡与ESCC之间关系密切。在此，我们旨在鉴定ESCC中与细胞焦亡相关的基因并构建预后风险模型。
从癌症基因组图谱（TCGA）数据库获取ESCC的RNA测序数据。采用基因集变异分析（GSVA）和基因集富集分析（GSEA）计算细胞焦亡相关通路评分（Pys）。使用加权基因共表达网络分析（WGCNA）和单因素Cox回归筛选与预后相关的细胞焦亡基因，并使用套索回归建立风险评分。最后，采用t检验比较模型与肿瘤-淋巴结-转移（TNM）分期之间的关系。此外，我们比较了低风险组和高风险组之间免疫浸润细胞和免疫检查点的差异。
使用WGCNA，283个基因与N分期和Pys显著相关。其中，单因素Cox分析表明83个基因与ESCC患者的预后相关。此后， 、 和 被确定为区分高风险组和低风险组的预后特征。高风险组和低风险组患者的T分期（P=0.018）和N分期（P<0.05）分布存在显著差异。此外，两组的免疫浸润细胞评分和免疫检查点表达也有显著差异。
我们的研究在ESCC中鉴定出3个与预后相关的细胞焦亡基因，并成功构建了一个预后模型。 、 和 3可能是ESCC中有前景的治疗靶点。
