He Chenglong, Dong Wenjing, Lyu Yanhua, Qin Yan, Zhong Siquan, Jiang Xiaomei, Xiao Jianjun
Department of Oncology, Zhongshan City People's Hospital, Zhongshan, Guangdong 528403, P.R. China.
Oncol Lett. 2024 Dec 5;29(2):89. doi: 10.3892/ol.2024.14835. eCollection 2025 Feb.
Colorectal cancer (CRC) is a malignant tumor with poor prognosis. Pyroptosis is a newly discovered type of programmed cell death that is typically accompanied by a strong inflammatory response. Accumulating evidence suggests that pyroptosis-related genes (PRGs) may have important roles in the development of malignant tumors. However, the association between PRG expression and clinical outcomes in CRC remain unclear. In the present study, the genetic variations and transcriptional patterns of 52 PRGs were comprehensively analyzed using cohorts from The Cancer Genome Atlas and Gene Expression Omnibus and the mRNA expression levels of 7 PRGs in collected CRC samples were validated using reverse transcription-quantitative PCR. Using LASSO-Cox analysis, a PRG score was then generated and the relationship between the PRG score and prognosis, immune cell infiltration and drug sensitivity in CRC was uncovered. In the present study, the mutation and expression patterns of PRGs were analyzed and it was found that these genes were differentially expressed in CRC tissues compared with normal tissues. Based on the expression patterns of the PRGs, patients with CRC were divided into two subtypes (cluster A and B), of which cluster B had an improved prognosis and a higher abundance of immune cells. Next, differentially expressed genes between clusters A and B were identified and a PRG risk score closely related to the prognosis of CRC was constructed. Then, a nomogram for evaluating the overall survival of patients was constructed. Furthermore, a low PRG risk score was characterized by immune activation and closely related to the microsatellite instability-high pattern. Additionally, the PRG risk score was notably correlated with drug sensitivity. In conclusion, the mutation and expression characteristics of PRGs in CRC were comprehensively analyzed and a prognostic PRG signature was constructed in the present study. This signature may predict immune cell infiltration and therapeutic response in CRC, providing new insights into the prognosis and treatment of CRC.
结直肠癌（CRC）是一种预后较差的恶性肿瘤。细胞焦亡是一种新发现的程序性细胞死亡类型，通常伴随着强烈的炎症反应。越来越多的证据表明，细胞焦亡相关基因（PRGs）可能在恶性肿瘤的发生发展中发挥重要作用。然而，PRG表达与CRC临床结局之间的关联仍不清楚。在本研究中，使用来自癌症基因组图谱（The Cancer Genome Atlas）和基因表达综合数据库（Gene Expression Omnibus）的队列对52个PRGs的基因变异和转录模式进行了全面分析，并使用逆转录定量PCR验证了收集的CRC样本中7个PRGs的mRNA表达水平。然后，通过LASSO-Cox分析生成PRG评分，并揭示了PRG评分与CRC预后、免疫细胞浸润和药物敏感性之间的关系。在本研究中，分析了PRGs的突变和表达模式，发现这些基因在CRC组织中与正常组织相比存在差异表达。根据PRGs的表达模式，将CRC患者分为两个亚型（A组和B组），其中B组预后较好且免疫细胞丰度较高。接下来，鉴定了A组和B组之间的差异表达基因，并构建了与CRC预后密切相关的PRG风险评分。然后，构建了评估患者总生存的列线图。此外，低PRG风险评分的特征是免疫激活，并且与微卫星高度不稳定模式密切相关。另外，PRG风险评分与药物敏感性显著相关。总之，本研究全面分析了CRC中PRGs的突变和表达特征，并构建了一个预后PRG特征。该特征可能预测CRC中的免疫细胞浸润和治疗反应，为CRC的预后和治疗提供新的见解。
