He Yayi, Song Lele, Wang Hao, Chen Peixin, Liu Yu, Sun Hui, Li Xiaobin, Dang Shiying, Liu Guifeng, Liu Xinyi, Chen Shifu, Zhang Xiaoni, Hofman Paul, Uchino Junji, Park Henry S, Pacheco Jose M, Tabbò Fabrizio, Xu Mingyan, Dai Jiawei, He Kan, Yang Yang, Zhou Caicun
Department of Medical Oncology Shanghai Pulmonary Hospital and Thoracic Cancer Institute Tongji University School of Medicine No. 507, Zhengmin Road, Yangpu District Shanghai 200433 P. R. China.
HaploX Biotechnology, Co., Ltd. 8th floor, Auto Electric Power Building, Songpingshan Road, Nanshan District Shenzhen Guangdong 518057 P. R. China.
Adv Sci (Weinh). 2020 Dec 30;8(4):2003263. doi: 10.1002/advs.202003263. eCollection 2021 Feb.
Evaluating the therapeutic response and survival of lung cancer patients receiving first-line chemotherapy has always been difficult. Limited biomarkers for evaluation exist and as a result histology represents an empiric tool to guide therapeutic decision making. In this study, molecular signatures associated with response and long-term survival of lung cancer patients receiving first-line chemotherapy are discovered. Whole-exome sequencing is performed on pretherapeutic tissue samples of 186 patients [145 non-small cell lung cancer (NSCLC) and 41 small cell lung cancer (SCLC)]. On the basis of genomic alteration characteristics, NSCLC patients can be classified into four subtypes (C1-C4). The long-term survival is similar among different subtypes. SCLC patients are also divided into four subtypes and significant difference in their progression free survival is revealed ( < 0.001). NSCLC patients can be divided into three subtypes (S1-S3) based on TMB. A trend of worse survival associated with higher TMB in subtype S3 than in S1+S2 is found. In contrast, no significant correlations between molecular subtype and therapeutic response are observed. In conclusion, this study identifies several molecular signatures associated with response and survival to first-line chemotherapy in lung cancer.
评估接受一线化疗的肺癌患者的治疗反应和生存率一直很困难。用于评估的生物标志物有限，因此组织学是指导治疗决策的一种经验性工具。在本研究中，发现了与接受一线化疗的肺癌患者的反应和长期生存相关的分子特征。对186例患者[145例非小细胞肺癌（NSCLC）和41例小细胞肺癌（SCLC）]的治疗前组织样本进行全外显子测序。根据基因组改变特征，NSCLC患者可分为四种亚型（C1-C4）。不同亚型的长期生存率相似。SCLC患者也分为四种亚型，其无进展生存期显示出显著差异（<0.001）。基于肿瘤突变负荷（TMB），NSCLC患者可分为三种亚型（S1-S3）。发现S3亚型中TMB较高者的生存趋势比S1+S2亚型更差。相比之下，未观察到分子亚型与治疗反应之间存在显著相关性。总之，本研究确定了几个与肺癌一线化疗反应和生存相关的分子特征。
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