The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China.
General Surgery, Cancer Center, Department of Breast Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, China.
Front Immunol. 2022 May 4;13:895110. doi: 10.3389/fimmu.2022.895110. eCollection 2022.
To identify molecular clusters associated with ferroptosis and to develop a ferroptosis-related signature for providing novel potential targets for the recurrence-free survival and treatment of breast cancer.
Ferroptosis-related gene (FRG) signature was constructed by univariate and multivariate Cox regression and least absolute shrinkage and selection operator (LASSO). Receiver operating characteristic curves, Kaplan-Meier survival analysis, principal component analysis, and univariate and multivariate Cox regression analyses in the training and test cohorts were used to evaluate the application of this signature. Quantitative reverse transcriptase-PCR (qRT-PCR) was employed to detect the expression of FRGs in the model. Furthermore, the correlations between the signature and immune microenvironment, somatic mutation, and chemotherapeutic drugs sensitivity were explored.
Internal and external validations affirmed that relapse-free survival differed significantly between the high-risk and low-risk groups. Univariate and multivariate Cox regression analyses indicated that the riskScore was an independent prognostic factor for BRCA. The areas under the curve (AUCs) for predicting 1-, 2-, and 3-year survival in the training and test cohorts were satisfactory. Significant differences were also found in the immune microenvironment and IC50 of chemotherapeutic drugs between different risk groups. Furthermore, we divided patients into three clusters based on 18 FRGs to ameliorate the situation of immunotherapy failure in BRCA.
The FRG signature functions as a robust prognostic predictor of the immune microenvironment and therapeutic response, with great potential to guide individualized treatment strategies in the future.
鉴定与铁死亡相关的分子簇，并构建铁死亡相关特征，为乳腺癌无复发生存和治疗提供新的潜在靶点。
采用单因素和多因素 Cox 回归以及最小绝对收缩和选择算子（LASSO）构建铁死亡相关基因（FRG）特征。在训练和测试队列中，采用受试者工作特征曲线、Kaplan-Meier 生存分析、主成分分析、单因素和多因素 Cox 回归分析来评估该特征的应用。采用定量逆转录-PCR（qRT-PCR）检测模型中 FRG 的表达。此外，还探讨了该特征与免疫微环境、体细胞突变和化疗药物敏感性的相关性。
内部和外部验证均证实，高风险组和低风险组之间的无复发生存差异显著。单因素和多因素 Cox 回归分析表明，风险评分是 BRCA 的独立预后因素。在训练和测试队列中，预测 1 年、2 年和 3 年生存率的曲线下面积（AUCs）均令人满意。不同风险组之间的免疫微环境和化疗药物 IC50 也存在显著差异。此外，我们基于 18 个 FRG 将患者分为三个聚类，以改善 BRCA 免疫治疗失败的情况。
FRG 特征可作为免疫微环境和治疗反应的强大预后预测因子，具有指导未来个体化治疗策略的巨大潜力。
