First Department of General Surgery, Xi'an Central Hospital, Xi'an, Shaanxi Province, China.
Department of digestive surgery, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, China.
Math Biosci Eng. 2021 Oct 14;18(6):8783-8796. doi: 10.3934/mbe.2021433.
Colorectal cancer (CRC), one of the most common malignancies worldwide, leads to abundant cancer-related mortalities annually. Pyroptosis, a new kind of programmed cell death, plays a critical role in immune response and tumor progression. Our study aimed to identify a prognostic signature for CRC based on pyroptosis-related genes (PRGs). The difference in PRGs between CRC tissues and normal tissues deposited in the TCGA database was calculated by "limma" R package. The tumor microenvironment (TME) of CRC cases was accessed by the ESTIMATE algorithm. The prognostic PRGs were identified using Cox regression analysis. A least absolute shrinkage and selector operation (LASSO) algorithm was used to calculate the risk scores and construct a clinical predictive model of CRC. Gene Set Enrichment Analysis (GSEA) was performed for understanding the function annotation of the signature in the tumor microenvironment. We found that most PRGs were significantly dysregulated in CRC. Through the LASSO method, three key PRGs were selected to calculate the risk scores and construct the prognostic model for CRC. The risk score was an independent indicator of patient's prognosis. In addition, we classified the CRC patients into two clusters based on risk scores and discovered that CRC patients in cluster 2 underwent worse overall survival and owned higher expression levels of immune checkpoint genes in tumor tissues. In conclusion, our study identified a PRG-related prognostic signature for CRC, according to which we classified the CRC patients into two clusters with distinct prognosis and immunotherapy potential.
结直肠癌(CRC)是全球最常见的恶性肿瘤之一,每年导致大量与癌症相关的死亡。细胞焦亡是一种新的程序性细胞死亡方式,在免疫反应和肿瘤进展中起着关键作用。我们的研究旨在基于细胞焦亡相关基因(PRGs)鉴定 CRC 的预后标志物。通过“limma”R 包计算 TCGA 数据库中 CRC 组织和正常组织之间 PRGs 的差异。通过 ESTIMATE 算法评估 CRC 病例的肿瘤微环境(TME)。通过 Cox 回归分析鉴定预后 PRGs。使用最小绝对收缩和选择算子(LASSO)算法计算风险评分并构建 CRC 的临床预测模型。进行基因集富集分析(GSEA)以了解该signature 在肿瘤微环境中的功能注释。我们发现大多数 PRGs 在 CRC 中明显失调。通过 LASSO 方法,选择了三个关键 PRGs 来计算风险评分并构建 CRC 的预后模型。风险评分是患者预后的独立指标。此外,我们根据风险评分将 CRC 患者分为两个聚类,并发现聚类 2 的 CRC 患者的总生存期更差,肿瘤组织中免疫检查点基因的表达水平更高。总之,我们根据 PRG 鉴定了一个与 CRC 相关的预后标志物,根据该标志物,我们将 CRC 患者分为具有不同预后和免疫治疗潜力的两个聚类。