School of Public Health, Wenzhou Medical University, Wenzhou 325035, China.
First Hospital Affiliated to Wenzhou Medical University, Wenzhou 325035, China.
Radiother Oncol. 2024 Jun;195:110259. doi: 10.1016/j.radonc.2024.110259. Epub 2024 Mar 26.
Radiotherapy is widely applied for lung adenocarcinoma (LUAD), while individualized differences led to different outcomes. This study aimed to establish a multi-gene risk scoring model to predict the benefits of LUAD patients from radiotherapy, based on different types of cell death respectively.
Other than autophagy, pyroptosis, ferroptosis and Immunogenic cell death (ICD), the LUAD prognostic model based on apoptosis had the best performance, and the area under curves (AUCs) of the receiver operating curve (ROC) for 1-, 3-, and 5-year OS were 0.700,0.736,0.723,respectively. Such genes were involved as SLC7A5, EXO1, ABAT, NLRP1 and GAR1. Then patients were divided into high and low risk groups by the median apoptosis-LUAD risk score. For patients in the high-risk group, i.e., the radiotherapy-tolerant group, we screened adjuvant chemotherapy and found that besides the conventional first-line chemotherapy regimen, drugs such as Fludarabine, Pevonedistat, and Podophyllotoxin Bromide may also have potential therapeutic value.
The multi-gene risk scoring model based on apoptosis might predict the radiotherapy benefits of LUAD patients and for those radioresistant patients classified by the model we also provided effective adjuvant chemicals, which would be used to guide clinical treatment.
放疗被广泛应用于肺腺癌(LUAD),但由于个体差异,导致疗效不同。本研究旨在分别建立基于不同细胞死亡类型的多基因风险评分模型,以预测 LUAD 患者从放疗中获益的情况。
除自噬、细胞焦亡、铁死亡和免疫原性细胞死亡(ICD)外,基于细胞凋亡的 LUAD 预后模型表现最佳,其 1、3、5 年 OS 的 ROC 曲线下面积(AUC)分别为 0.700、0.736 和 0.723。涉及的基因有 SLC7A5、EXO1、ABAT、NLRP1 和 GAR1。然后,患者根据中位数凋亡-LUAD 风险评分分为高风险和低风险组。对于高风险组(即放疗耐受组)的患者,我们筛选了辅助化疗药物,发现除了常规的一线化疗方案外,氟达拉滨、Pevonedistat 和鬼臼毒素溴化物等药物也可能具有潜在的治疗价值。
基于细胞凋亡的多基因风险评分模型可能预测 LUAD 患者的放疗获益情况,对于模型分类的放疗抵抗患者,我们也提供了有效的辅助化疗药物,以指导临床治疗。