Li Zhufeng, Yuan Fang, Liu Xin, Wei Jianming, Liu Tong, Li Weidong, Li Chuan
Department of General Surgery, Tianjin Medical University General Hospital, Tianjin, China.
Department of Anesthesiology, Tianjin Medical University General Hospital, Tianjin, China.
Front Oncol. 2023 May 23;13:1201616. doi: 10.3389/fonc.2023.1201616. eCollection 2023.
Ferroptosis, a novel form of regulating cell death, is related to various cancers. However, the role of ferroptosis-related genes (FRGs) on the occurrence and development of colon cancer (CC) needs to be further elucidated.
CC transcriptomic and clinical data were downloaded from TCGA and GEO databases. The FRGs were obtained from the FerrDb database. The consensus clustering was performed to identify the best clusters. Then, the entire cohort was randomly divided into the training and testing cohorts. Univariate Cox, LASSO regression and multivariate Cox analyses were used to construct a novel risk model in training cohort. The testing and the merged cohorts were performed to validate the model. Moreover, CIBERSORT algorithm analyze TIME between high- and low- risk groups. The immunotherapy effect was evaluated by analyzing the TIDE score and IPS between high- and low- risk groups. Lastly, RT-qPCR were performed to analyze the expression of the three prognostic genes, and the 2-years OS and DFS between the high- and low- risk groups of 43 clinical CC samples to further validate the value of the risk model.
SLC2A3, CDKN2A, and FABP4 were identified to construct a prognostic signature. Kaplan-Meier survival curves showed that OS between the high- and low-risk groups were statistically significant (p<0.001, p<0.001, p<0.001). TIDE score and IPS were higher in the high-risk group (p<0.005, p<0.005, p<0.001, p = 3e-08, p = 4.1e-10). The clinical samples were divided into high- and low- risk groups according to the risk score. There was a statistical difference in DFS (p=0.0108).
This study established a novel prognostic signature and provided more insight into the immunotherapy effect of CC.
铁死亡是一种新型的细胞死亡调控形式，与多种癌症相关。然而，铁死亡相关基因（FRGs）在结肠癌（CC）发生发展中的作用尚需进一步阐明。
从TCGA和GEO数据库下载CC转录组和临床数据。从FerrDb数据库获取FRGs。进行一致性聚类以确定最佳聚类。然后，将整个队列随机分为训练队列和测试队列。在训练队列中使用单因素Cox、LASSO回归和多因素Cox分析构建一个新的风险模型。在测试队列和合并队列中对该模型进行验证。此外，使用CIBERSORT算法分析高风险组和低风险组之间的肿瘤免疫微环境（TIME）。通过分析高风险组和低风险组之间的TIDE评分和免疫预测评分（IPS）评估免疫治疗效果。最后，进行RT-qPCR分析三个预后基因的表达，并分析43例临床CC样本高风险组和低风险组之间的2年总生存期（OS）和无病生存期（DFS），以进一步验证风险模型的价值。
鉴定出溶质载体家族2成员3（SLC2A3）、细胞周期蛋白依赖性激酶抑制剂2A（CDKN2A）和脂肪酸结合蛋白4（FABP4）以构建一个预后特征。Kaplan-Meier生存曲线显示，高风险组和低风险组之间的OS具有统计学意义（p<0.001，p<0.001，p<0.001）。高风险组的TIDE评分和IPS更高（p<0.005，p<0.005，p<0.001，p = 3e-08，p = 4.1e-10）。根据风险评分将临床样本分为高风险组和低风险组。DFS存在统计学差异（p = 0.0108）。
本研究建立了一种新的预后特征，并为CC的免疫治疗效果提供了更多见解。
