Comprehensive characterization of early-onset lung cancer, in Chinese young adults

Ye Tian, Rui Ma, Wenchang Zhao, Shumin Wang, Chuanjiang Zhou, Weibing Wu, Bo Yang, Hua Xin, Hongyan Wang, Pengfei Li, Ranhua Li, Changhong Liu, Yao Lu, Qian Yu, Chengyang Song, Han Zhang, Ruipu Liang, Lei Zhang, Di Zhou, Xitong Zhao, Zhuo Wu, Yafei Qi, Rui Wang, Teng Fei () and Xueying Yang ()
Additional contact information
Ye Tian: The Fourth Affiliated Hospital of China Medical University
Rui Ma: The Fourth Affiliated Hospital of China Medical University
Wenchang Zhao: Northeastern University
Shumin Wang: General Hospital of Northern Theater Command
Chuanjiang Zhou: Benxi Central Hospital
Weibing Wu: The First Affiliated Hospital of Nanjing Medical University
Bo Yang: Chinese PLA General Hospital
Hua Xin: China-Japan Union Hospital of Jilin University
Hongyan Wang: The Fourth Affiliated Hospital of Hebei Medical University
Pengfei Li: Yanan Center Hospital
Ranhua Li: Kunming Medical University First Affiliated Hospital
Changhong Liu: The Second Hospital of Dalian Medical University
Yao Lu: The Fourth Affiliated Hospital of China Medical University
Qian Yu: The Fourth Affiliated Hospital of China Medical University
Chengyang Song: The Fourth Affiliated Hospital of China Medical University
Han Zhang: Northeastern University
Ruipu Liang: Northeastern University
Lei Zhang: The Fourth Affiliated Hospital of China Medical University
Di Zhou: The Fourth Affiliated Hospital of China Medical University
Xitong Zhao: The Fourth Affiliated Hospital of China Medical University
Zhuo Wu: The Fourth Affiliated Hospital of China Medical University
Yafei Qi: Shengjing Hospital of China Medical University
Rui Wang: The Fourth Affiliated Hospital of China Medical University
Teng Fei: Northeastern University
Xueying Yang: The Fourth Affiliated Hospital of China Medical University

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-57309-4

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