Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.
Department of Experimental Research, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, China.
J Natl Cancer Inst. 2021 Apr 6;113(4):471-480. doi: 10.1093/jnci/djaa100.
Induction chemotherapy (IC) followed by concurrent chemoradiotherapy is the mainstay treatment for patients with locoregionally advanced nasopharyngeal carcinoma. However, some patients obtain little benefit and experience unnecessary toxicities from IC. We intended to develop a gene-expression signature that can identify beneficiaries of IC.
We screened chemosensitivity-related genes by comparing gene-expression profiles of patients with short-term tumor response or nonresponse to IC (n = 95) using microarray analysis. Chemosensitivity-related genes were quantified by digital expression profiling in a training cohort (n = 342) to obtain a gene signature. We then validated this gene signature in the clinical trial cohort (n = 187) and an external independent cohort (n = 240). Tests of statistical significance are 2-sided.
We identified 43 chemosensitivity-related genes associated with the short-term tumor response to IC. In the training cohort, a 6-gene signature was developed that was highly accurate at predicting the short-term tumor response to IC (area under the curve [AUC] = 0.87, sensitivity = 87.5%, specificity = 75.6%). We further found that IC conferred failure-free survival benefits only in patients in the benefit group (hazard ratio [HR] = 0.54, 95% confidence interval [CI] = 0.34 to 0.87; P = .01) and not on those in the no-benefit group (HR = 1.25, 95% CI = 0.62 to 2.51; P = .53). In the clinical trial cohort, the 6-gene signature was also highly accurate at predicting the tumor response (AUC = 0.82, sensitivity = 87.5%, specificity = 71.8%) and indicated failure-free survival benefits. In the external independent cohort, similar results were observed.
The 6-gene signature can help select beneficiaries of IC and lay a foundation for a more individualized therapeutic strategy for locoregionally advanced nasopharyngeal carcinoma patients.
诱导化疗（IC）联合同期放化疗是局部晚期鼻咽癌患者的主要治疗方法。然而，一些患者从 IC 中获益甚少，且经历了不必要的毒性反应。我们旨在开发一种基因表达谱，以识别 IC 的获益者。
我们通过微阵列分析比较了短期肿瘤反应或无反应的患者的基因表达谱，筛选出与化疗敏感性相关的基因（n=95）。在训练队列（n=342）中通过数字表达谱定量检测化疗敏感性相关基因，以获得基因特征。然后在临床试验队列（n=187）和外部独立队列（n=240）中验证该基因特征。统计显著性检验为双侧检验。
我们确定了 43 个与 IC 短期肿瘤反应相关的化疗敏感性相关基因。在训练队列中，开发了一个 6 基因特征，该特征对 IC 的短期肿瘤反应具有很高的预测准确性（曲线下面积[AUC]为 0.87，敏感性为 87.5%，特异性为 75.6%）。我们还发现，IC 仅在获益组患者中提供无复发生存获益（风险比[HR]为 0.54，95%置信区间[CI]为 0.34 至 0.87；P=0.01），而在无获益组患者中没有获益（HR=1.25，95%CI 为 0.62 至 2.51；P=0.53）。在临床试验队列中，6 基因特征也具有很高的预测肿瘤反应的准确性（AUC=0.82，敏感性为 87.5%，特异性为 71.8%），并提示无复发生存获益。在外部独立队列中也观察到类似的结果。
该 6 基因特征可帮助选择 IC 的获益者，并为局部晚期鼻咽癌患者的更个体化治疗策略奠定基础。
