Chang Kaili, Yuan Chong, Liu Xueguang
Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Front Oncol. 2021 Apr 30;11:649347. doi: 10.3389/fonc.2021.649347. eCollection 2021.
As a type of regulated cell death induced by Ras selective lethal (RSL) compounds such as erasti, ferroptosis is characterized by iron-dependent lipid peroxide accumulation to lethal levels. At present, little is known about the role of ferroptosis-related genes in clear-cell renal cell carcinoma (ccRCC). In the present study, the expression data of ferroptosis-related genes in ccRCC were obtained from the Cancer Genome Atlas (TCGA), and COX regression analysis was performed to construct a risk model of ferroptosis prognostic signature. The GEO database was used to verify the accuracy of the model. The following findings were made: the results reveal that the prognostic signature constructed by 11 ferroptosis genes (CARS, CD44, DPP4, GCLC, HMGCR, HSPB1, NCOA4, SAT1, PHKG2, GOT1, HMOX1) was significantly related to the overall survival (OS) of ccRCC patients based on the lowest Akaike information criterion (AIC); multivariate analysis indicates that ferroptosis-related gene prognostic signature was an independent prognostic factor in ccRCC patients; the calibration curve and c-index value (0.77) demonstrate that the nomogram with the signature could predict the survival of ccRCC patients; and enrichment analysis shows that the high-risk group were enriched in humoral immunity and receptor interaction pathways. The aforementioned findings indicate that the ferroptosis-related gene signature can accurately predict the prognosis of ccRCC patients and provide valuable insights for individualized treatment.
作为一种由如erasti等Ras选择性致死（RSL）化合物诱导的程序性细胞死亡，铁死亡的特征是铁依赖性脂质过氧化物积累至致死水平。目前，关于铁死亡相关基因在透明细胞肾细胞癌（ccRCC）中的作用知之甚少。在本研究中，从癌症基因组图谱（TCGA）获取ccRCC中铁死亡相关基因的表达数据，并进行COX回归分析以构建铁死亡预后特征的风险模型。利用GEO数据库验证该模型的准确性。得到以下结果：结果显示，基于最低赤池信息准则（AIC），由11个铁死亡基因（CARS、CD44、DPP4、GCLC、HMGCR、HSPB1、NCOA4、SAT1、PHKG2、GOT1、HMOX1）构建的预后特征与ccRCC患者的总生存期（OS）显著相关；多因素分析表明，铁死亡相关基因预后特征是ccRCC患者的独立预后因素；校准曲线和c指数值（0.77）表明，带有该特征的列线图可预测ccRCC患者的生存情况；富集分析显示，高危组在体液免疫和受体相互作用途径中富集。上述结果表明，铁死亡相关基因特征可准确预测ccRCC患者的预后，并为个体化治疗提供有价值的见解。
