Zhang Bin, Zhang Lianmin, Yue Dongsheng, Li Chenguang, Zhang Hua, Ye Junyi, Gao Liuwei, Zhao Xiaoliang, Chen Chen, Huo Yansong, Pang Chong, Li Yue, Chen Yulong, Chuai Shannon, Zhang Zhenfa, Giaccone Giuseppe, Wang Changli
Department of Lung Cancer, Tianjin Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China.
Burning Rock Biotech, Guangzhou, China.
Transl Lung Cancer Res. 2020 Aug;9(4):1187-1201. doi: 10.21037/tlcr-19-664.
The genomic profile of non-small cell lung cancer (NSCLC) in Asians is distinct from that of Caucasians, but comprehensive genetic profiling reports have been limited for Asian patients. We aimed to elucidate genomic characteristics of Chinese NSCLC patients and develop potential model including genomic characteristics to predict postoperative prognosis.
Resected tumor samples from 511 patients with stage I-IV lung cancer were subjected to targeted sequencing using a panel of 295 cancer-related genes. Based on the molecular profiles and clinical features, we established nomogram models with predictors consisting of integrated clinical and genomic characteristics to provide post-operative risk stratification.
Compared to the TCGA population (mainly Caucasians), there was a significantly higher frequency of (53.7% 14.4%) and (8.4% 1.3%) mutations and less mutated (11.0% 32.6%), (4.4% 17.4%) and (16.3% 29.6%) in Chinese lung adenocarcinomas (LUAD). Distinct patterns of mutually exclusive and co-occurring mutations were identified between LUAD and lung squamous cell carcinoma (LUSC), indicating the unique histology-specific tumorigenesis mechanism of each subtype. We observed alterations in pathways correlated with clinical characteristics. Additionally, we constructed nomogram model with predictors consisting of clinical and genomic characteristics, which were more accurate than models with clinical characteristics or TNM staging only both in stage I-IIIA patients and T1-2N0M0 sub-cohort.
This study revealed Chinese NSCLC patients have unique genomic profile. Furthermore, the nomogram model combining clinical features with genomic characteristics could improve risk stratification in early-stage NSCLC.
亚洲非小细胞肺癌（NSCLC）的基因组特征与白种人不同，但针对亚洲患者的全面基因特征分析报告有限。我们旨在阐明中国NSCLC患者的基因组特征，并开发包括基因组特征在内的潜在模型以预测术后预后。
对511例I-IV期肺癌患者切除的肿瘤样本进行靶向测序，使用包含295个癌症相关基因的基因panel。基于分子特征和临床特征，我们建立了列线图模型，其预测因子由综合临床和基因组特征组成，以提供术后风险分层。
与TCGA人群（主要为白种人）相比，中国肺腺癌（LUAD）中 （53.7% 对14.4%）和 （8.4% 对1.3%）突变的频率显著更高，而 （11.0% 对32.6%）、 （4.4% 对17.4%）和 （16.3% 对29.6%）突变较少。在LUAD和肺鳞状细胞癌（LUSC）之间鉴定出互斥和共发生突变的不同模式，表明每种亚型具有独特的组织学特异性肿瘤发生机制。我们观察到与临床特征相关的通路改变。此外，我们构建了由临床和基因组特征组成预测因子的列线图模型，在I-IIIA期患者和T1-2N0M0亚组中，该模型比仅具有临床特征或TNM分期的模型更准确。
本研究表明中国NSCLC患者具有独特的基因组特征。此外，将临床特征与基因组特征相结合的列线图模型可改善早期NSCLC的风险分层。
