Comprehensive characterization of early-onset lung cancer, in Chinese young adults
Ye Tian, Rui Ma, Wenchang Zhao, Shu Min Wang, Chuanjiang Zhou, Weibing Wu, Bo Yang, Hua Xin, Hongyan Wang, Pengfei Li, Ranhua Li, Changhong Liu, Yao Lü, Yu Qian, Chengyang Song, Han Zhang, Ruipu Liang, Lei Zhang, Di Zhou, Xitong Zhao, Zhuo Wu, Yafei Qi, Rui Wang, Fei Teng, Xueying Yang
Abstract
Early-onset lung cancer in young adults represents a less studied clinical entity with increasing incidence which still affects a large number of cancer patients. Here we perform a comprehensive analysis of early-onset lung cancer for the clinicopathological features, genomic alterations, gene expression, and immune landscape by establishing a cohort enrolling 421 non-small cell lung cancer (NSCLC) patients from ten medical centers in China. Comparative analysis reveals a distinct genomic alteration between younger and elder patients with NSCLC, with ERBB2 mutations and ALK-rearrangement strikingly more frequent in younger group. Transcriptome profiling indicates altered cellular metabolism and immune-related genes in tumors from younger patients. Immunological analysis reveals a decreased infiltration of immune cells (notably T cells) in tumors from younger patients. Cellular and mechanistic studies show that the prevalent ERBB2 mutants in cancer from younger patients can indeed drive tumorigenesis by elevating AKT signaling. Importantly, meta-analysis of clinical trials and our clinical practice further validate the promise of HER2-targeted therapy to treat early-onset NSCLC in East Asian patients. Our comprehensive and integrative analysis not only reveal multiple unrecognized characteristics of early-onset lung cancer, but also inform actionable therapeutics to manage this type of cancer. Early-onset lung cancer in young adults remains poorly studied. Here, the authors analyse the clinicopathological, molecular, and immune features of early-onset non-small cell lung cancers in a cohort of 421 patients across ten medical centres in China, identifying potential therapeutic strategies for this subgroup.