Department of Gastrointestinal Surgery II, Key Laboratory of Hubei Province for Digestive System Disease, Renmin Hospital, Wuhan University, Wuhan, Hubei Province, China.
Clin Exp Med. 2021 Aug;21(3):467-477. doi: 10.1007/s10238-021-00697-w. Epub 2021 Mar 6.
Ferroptosis is a newly discovered programmed cell death that plays a vital role in the occurrence and development of tumors. However, little is known about its prognostic value of ferroptosis-related genes (FRGs) in colorectal cancer (CRC). This study was to investigate the clinical significance of FRGs on overall survival (OS) of patients with CRC. The mRNA expression profiles and corresponding clinical data of CRC patients were downloaded from public databases. Least absolute shrinkage and selection operator (LASSO) Cox regression was applied to identify hub FRGs and establish a novel ferroptosis-related gene signature in predicting OS in training cohort, and assessed in the validation cohort. Then, the genomic-clinicopathologic nomogram integrating risk scores and clinicopathological features were established. Thirteen FRGs were identified to be most significantly related to the OS of CRC patients. Based on the LASSO Cox regression algorithm, we selected 10 genes from 13 FRGs to establish a prognostic risk signature. The log-rank test and Kaplan-Meier analysis confirmed the predictive value of the risk scores for OS in CRC patients. The time-dependent receiver operating characteristic (tdROC) of signature indicates the showed powerful prediction ability in both training cohort and validation cohort. Then, a genomic-clinicopathologic nomogram integrating age, stage, and risk scores was established and demonstrated high predictive accuracy and clinical value, which was validated through tdROC and calibration curves. The ferroptosis-related gene signature and genomic-clinicopathologic nomogram could be used to predict the prognosis of CRC patients and might also be potential therapeutic targets.
铁死亡是一种新发现的程序性细胞死亡，在肿瘤的发生和发展中起着至关重要的作用。然而，关于铁死亡相关基因（FRGs）在结直肠癌（CRC）中的预后价值知之甚少。本研究旨在探讨 FRGs 对 CRC 患者总生存期（OS）的临床意义。从公共数据库中下载了 CRC 患者的 mRNA 表达谱和相应的临床数据。最小绝对收缩和选择算子（LASSO）Cox 回归用于识别枢纽 FRGs，并在训练队列中建立预测 OS 的新型铁死亡相关基因特征，并在验证队列中进行评估。然后，建立了整合风险评分和临床病理特征的基因组-临床病理列线图。确定了 13 个 FRGs 与 CRC 患者的 OS 最显著相关。基于 LASSO Cox 回归算法，我们从 13 个 FRGs 中选择了 10 个基因来建立预后风险特征。对数秩检验和 Kaplan-Meier 分析证实了风险评分对 CRC 患者 OS 的预测价值。特征的时间依赖性接收者操作特征（tdROC）表明，该特征在训练队列和验证队列中均具有强大的预测能力。然后，建立了一个整合年龄、分期和风险评分的基因组-临床病理列线图，并通过 tdROC 和校准曲线验证了其具有较高的预测准确性和临床价值。铁死亡相关基因特征和基因组-临床病理列线图可用于预测 CRC 患者的预后，也可能是潜在的治疗靶点。
