| Title | Disparate genomic characteristics of patients with early-stage lung adenocarcinoma manifesting as radiological subsolid or solid lesions |
| Authors | Li, Hao Sun, Zewen Li, Yanmeng Qi, Qingyi Huang, Haiyan Wang, Xuan Zhou, Jian Liu, Ke Yin, Ping Wang, Zhenfan Li, Xiao Yang, Fan |
| Affiliation | Peking Univ Peoples Hosp, Dept Thorac Surg, 11 Xizhimen South St, Beijing 100044, Peoples R China Peking Univ, Biomed Pioneering Innovat Ctr BIOPIC, Sch Life Sci, Beijing 100871, Peoples R China Peking Univ, Dept Thorac Surg, Peoples Hosp, Beijing 100871, Peoples R China Peking Univ Peoples Hosp, Dept Radiol, Beijing 100044, Peoples R China Berry Oncol Corp, 4 Sci Pk Rd, Beijing 102206, Peoples R China Peking Univ Peoples Hosp, Dept Cardiac Surg, Beijing 100044, Peoples R China |
| Keywords | GROUND-GLASS OPACITY CANCER PROGRESSION MODELS PROGNOSTIC IMPACT 8TH EDITION HETEROGENEITY NODULES CLASSIFICATION MANAGEMENT INFERENCE COMPONENT |
| Issue Date | Apr-2022 |
| Publisher | LUNG CANCER |
| Abstract | Introduction: Early-stage lung adenocarcinoma (LUAD) manifesting as subsolid nodules (SSNs) exhibit more favorable prognosis than solid nodules (SNs). However, the genomic underpinnings behind their indolent tumor behavior remain largely unexplained.& nbsp;Methods: We identified patients with stage I invasive LUAD who underwent complete surgical resection and broad-panel next-generation sequencing (NGS). Comparative genomic profiling was then performed by radiological subtype (SSNs vs. SNs) regarding the general genomic features, driver genes, oncogenic pathways, therapeutic actionability, and evolutionary trajectory.& nbsp;Results: In total, 177 SSN-LUADs and 133 SN-LUADs were included. Compared with SNs, SSN-LUADs possessed lower somatic mutation count (P < 0.001), genomic alteration count (P = 0.002), and intra-tumor heterogeneity (P = 0.006). In terms of driver genes, SSNs harbored more EGFR mutation (77% vs. 62%), but had lower frequencies of genes such as TP53, ARID1A, PIK3CA, CDKN2A, and BRAF (FDR q < 0.1). Besides, RBM10 mutation was independently associated with SSN-LUADs in multivariate analysis (P = 0.033). Three oncogenic pathways (p53, cell cycle, PI3K) were altered with statistical significance in SNs, while only RNA splicing/processing pathway was significantly altered in SSNs (FDR q < 0.1). Also, SSNs had significantly lower number of pathway alterations (P < 0.001). Finally, SSNs and SNs showed distinct evolutionary trajectories regarding somatic mutations during early-stage LUAD progression.& nbsp;Conclusions: This study performed the first direct comparative genomic profiling in pathologic stage I invasive LUAD by radiological subtype, highlighting a less complex genomic architecture of SSNs, which might be the molecular interpretation of their indolent tumor behavior. |
| URI | http://hdl.handle.net/20.500.11897/646436 |
| ISSN | 0169-5002 |
| DOI | 10.1016/j.lungcan.2022.02.012 |
| Indexed | SCI(E) |
| Appears in Collections: | 人民医院 生命科学学院 |
