Department of Gastroenterology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanghai Key Laboratory of Gut Microecology and Associated Major Diseases Research, Center for Digestive Diseases Research and Clinical Translation of Shanghai Jiao Tong University, China.
Technol Cancer Res Treat. 2024 Jan-Dec;23:15330338241277584. doi: 10.1177/15330338241277584.
Pyroptosis is a programmed cell death, which garners increasing attention by relating to immune and therapy response. However, the role of pyroptosis in colorectal cancer (CRC) remains unclear. Our study mainly to explore the role of pyroptosis in CRC. The mRNA expression data and corresponding clinical information of CRC patients were achieved from The Cancer Genome Atlas (TCGA). Pyroptosis-related genes (PRGs) were identified using DESeq2 R package and biological function was analyzed using cluster Profiler R package. A PRGs-based prognosis model was constructed by a univariate Cox and LASSO regression analyses. Then, the affecting of risk signature to clinicopathological characteristics, immune status and infiltrated immune cells, immune checkpoint and chemotherapy sensitivity was analyzed. qRT-PCR and IHC were performed for the expression level of PRGs. Moreover, a nomogram predict model was constructed. Total 57 PRGs were identified between 500 CRC samples and 44 normal samples. Those PRGs mainly enriched in immune-related and pyroptosis-related pathways. GABRD, NADK, TMEM240, RER1, AGRN, UBE2J2, CALML6, PLCH2, TMEM88B have been identified as gene signature and a prognostic model was constructed and validated. CRC patients with high-risk score showed poor survival, high TMB score, high proportion of CD4 + memory T cells, common lymphoid progenitors, cancer associated fibroblasts, mast cells, and neutrophils. The immune checkpoint related genes, CD160, CD200R1, CD244, CD28, CD40LG, CD44, CD48, CD80, CD86, HHLA2, ICOS, IDO1, TIGIT, TNFRSF25, TNFRSF4, TNFRSF9, TNFSF15, TNFSF18 also increased in high-risk score group. CRC patients with high-risk score more sensitive to docetaxel and rapamycin but resistance to gemcitabine and mitomycin. Moreover, a predictive nomogram for 1-, 3-, 5-year for CRC patients was established and validated. In the study, a PRGs-based prognostic model and a predictive model were constructed. These models are effective and robust in prediction the 1-, 3-, and 5-year survival of CRC patients.
细胞焦亡是一种程序性细胞死亡，与免疫和治疗反应有关，因此越来越受到关注。然而，细胞焦亡在结直肠癌（CRC）中的作用尚不清楚。本研究主要探讨细胞焦亡在 CRC 中的作用。从癌症基因组图谱（TCGA）中获得了 CRC 患者的 mRNA 表达数据和相应的临床信息。使用 DESeq2 R 包鉴定细胞焦亡相关基因（PRGs），并使用 cluster Profiler R 包分析其生物学功能。通过单因素 Cox 和 LASSO 回归分析构建基于 PRGs 的预后模型。然后，分析风险特征对临床病理特征、免疫状态和浸润免疫细胞、免疫检查点和化疗敏感性的影响。进行 qRT-PCR 和 IHC 以检测 PRGs 的表达水平。此外，构建了一个列线图预测模型。在 500 例 CRC 样本和 44 例正常样本之间鉴定出 57 个 PRGs。这些 PRGs 主要富集在免疫和细胞焦亡相关途径中。GABRD、NADK、TMEM240、RER1、AGR、UBE2J2、CALML6、PLCH2、TMEM88B 已被确定为基因特征，并构建和验证了预后模型。高风险评分的 CRC 患者生存不良，TMB 评分高，CD4+记忆 T 细胞、常见淋巴祖细胞、癌症相关成纤维细胞、肥大细胞和中性粒细胞比例高。免疫检查点相关基因 CD160、CD200R1、CD244、CD28、CD40LG、CD44、CD48、CD80、CD86、HHLA2、ICOS、IDO1、TIGIT、TNFRSF25、TNFRSF4、TNFRSF9、TNFSF15、TNFSF18 在高风险评分组中也增加。高风险评分的 CRC 患者对多西他赛和雷帕霉素更敏感，但对吉西他滨和丝裂霉素耐药。此外，还建立并验证了用于预测 CRC 患者 1、3、5 年的列线图预测模型。在这项研究中，构建了基于 PRGs 的预后模型和预测模型。这些模型在预测 CRC 患者 1、3 和 5 年生存率方面是有效和稳健的。
