Liu Yutao, Xu Fang, Wang Yubo, Wu Qingchen, Wang Buhai, Yao Yanwen, Zhang Yu, Han-Zhang Han, Ye Junyi, Zhang Lu, Mao Xinru, Zhang Zhe, Liu Jing, Zhu Liangjun, Guo Renhua
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China.
Department of Thoracic Medicine, Hunan Cancer Center and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410006, P.R. China.
Oncol Lett. 2019 Sep;18(3):3159-3169. doi: 10.3892/ol.2019.10625. Epub 2019 Jul 16.
Currently, in clinical settings, all mutations have been considered equally. However, numerous studies have demonstrated that the position and type of mutation have differential effects on prognosis. Such discrepancy can be partially due to the lack of unifying classification system for mutations. In the present study, two of the most frequently used systems were compared, according to the location of the mutation or its functional effects on p53 protein and the impact of mutations on the overall survival (OS) time of 379 Chinese patients with advanced lung cancer was analyzed. Capture-based ultra-deep targeted sequencing on plasma samples of 379 patients with advanced lung cancer was performed. The present results suggested that mutations occurring in exon 8 may be associated with shorter OS in tyrosine kinase inhibitor-naïve patients (P=0.013) and in patients previously treated with one line of treatment (P=0.032). The results of the present study provided solid evidence that not all mutations were associated with a similar prognosis. Mutations in exon 8 were found in a subgroup of patients with unfavorable prognosis across various treatment histories. To the best of our knowledge, the present study is the first to compare different mutation classification systems in a large cohort of patients with advanced lung cancer.
目前，在临床环境中，所有突变都被同等看待。然而，大量研究表明，突变的位置和类型对预后有不同影响。这种差异部分可能是由于缺乏统一的突变分类系统。在本研究中，根据突变的位置或其对p53蛋白的功能影响，比较了两种最常用的系统，并分析了突变对379例中国晚期肺癌患者总生存（OS）时间的影响。对379例晚期肺癌患者的血浆样本进行了基于捕获的超深度靶向测序。目前的结果表明，外显子8中发生的突变可能与未接受过酪氨酸激酶抑制剂治疗的患者（P=0.013）以及先前接受过一线治疗的患者（P=0.032）的较短OS相关。本研究结果提供了确凿证据，表明并非所有突变都与相似的预后相关。在具有不同治疗史的预后不良患者亚组中发现了外显子8中的突变。据我们所知，本研究是首次在一大群晚期肺癌患者中比较不同的突变分类系统。
