Department of Oncology, Xinqiao Hospital, Army Medical University, Chongqing, 400037, China.
Key Laboratory of Immunotherapy, Xinqiao Hospital, The Third Military Medical University, Chongqing, 400037, China.
Commun Biol. 2021 Jan 29;4(1):131. doi: 10.1038/s42003-021-01657-6.
Therapeutic radiation can result in substantially different survival outcomes for patients with non-small cell lung cancer (NSCLC). Measures for identification of patients who can benefit most throughout radiotherapy remain limited. In this retrospective study, survival analysis was performed based on a discovery cohort from TCGA and a validation cohort from three independent hospitals. Tumor mutational burden (TMB) and chromosomal aneuploidy (ANE) were derived from the whole exome sequencing (WES) data from treatment-naïve tumors. Integrated risk scores were derived from TMB and ANE by a multivariate Cox proportional hazards model. TCGA reveal that TMB and ANE are associated positively and negatively, respectively, with survival throughout radiotherapy. Additionally, the synergistically predictive significance of these two genomic alterations, in differing responders and non-responders to radiotherapy is identified. These biomarkers may have clinical potential to improve personalized treatment management by rationally identifying highly likely responders to therapeutic radiation in patients with NSCLC.
治疗性放疗可能会对非小细胞肺癌 (NSCLC) 患者产生截然不同的生存结果。目前仍缺乏用于识别放疗中获益最大的患者的方法。在这项回顾性研究中，基于 TCGA 的发现队列和三个独立医院的验证队列进行了生存分析。肿瘤突变负担 (TMB) 和染色体非整倍性 (ANE) 是从治疗前肿瘤的全外显子测序 (WES) 数据中得出的。通过多变量 Cox 比例风险模型，从 TMB 和 ANE 中得出综合风险评分。TCGA 表明，TMB 和 ANE 分别与放疗期间的生存呈正相关和负相关。此外，还确定了这两种基因组改变在不同放疗反应者和非反应者中的协同预测意义。这些生物标志物可能具有临床潜力，通过合理识别 NSCLC 患者中极有可能对治疗性放疗有反应的患者，改善个体化治疗管理。
