Comprehensive characterization of early-onset lung cancer, in Chinese young adults
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.
Authors
- Ranhua Li
- Chengyang Song
- R.R. Liang (ORCID: https://orcid.org/0000-0002-1419-0234)
- Yu Qian (ORCID: https://orcid.org/0000-0001-9742-3330)
- Di Zhou
- Zhuo Wu (ORCID: https://orcid.org/0000-0002-2654-5362)
- Wenchang Zhao (ORCID: https://orcid.org/0000-0003-1899-7016)
- Yafei Qi (ORCID: https://orcid.org/0000-0002-5784-1463)
- Lei Zhang (ORCID: https://orcid.org/0000-0003-3944-5691)
- Yao Lü (ORCID: https://orcid.org/0000-0002-3380-7762)
- Pengfei Li (ORCID: https://orcid.org/0000-0002-3044-7976)
- Hongyan Wang (ORCID: https://orcid.org/0000-0002-8337-0968)
- Han Zhang (ORCID: https://orcid.org/0000-0002-2684-512X)
- Rui Wang (ORCID: https://orcid.org/0000-0003-1723-4746)
- Ye Tian (ORCID: https://orcid.org/0000-0001-6700-4098)
- Fei Teng (ORCID: https://orcid.org/0000-0001-9620-0450)
- Hua Xin (ORCID: https://orcid.org/0000-0002-8406-1921)
- Xueying Yang (ORCID: https://orcid.org/0009-0000-1787-7229)
- Rui Ma (ORCID: https://orcid.org/0009-0000-6191-2159)
- Changhong Liu (ORCID: https://orcid.org/0000-0002-0906-9069)
- Weibing Wu
- Xitong Zhao
- Shu Min Wang (ORCID: https://orcid.org/0000-0003-4489-9794)
- Chuanjiang Zhou
Institutions
- Hebei Medical University (CN)
- Union Hospital (HK)
- Dalian Medical University (CN)
- Jilin University (CN)
- Kunming Medical University (CN)
- Chinese PLA General Hospital (CN)
- Xian Central Hospital (CN)
- Yanan University Affiliated Hospital (CN)
- Fourth Affiliated Hospital of China Medical University (CN)
- Second Affiliated Hospital of Dalian Medical University (CN)
- Fourth Hospital of Hebei Medical University (CN)
- First Affiliated Hospital of Kunming Medical University (CN)
- General Hospital of Shenyang Military Region (CN)
- Jiangsu Province Hospital (CN)
- Nanjing Medical University (CN)
- China Medical University (CN)
- Northeastern University (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-02-26
- DOI
- https://doi.org/10.1038/s41467-025-57309-4
- Citations
- 16
- Primary Topic
- Lung Cancer Treatments and Mutations
- Type
- article
- Field-Weighted Citation Impact
- 24.29
Funders
- National Natural Science Foundation of China
- Natural Science Foundation of Liaoning Province
- Department of Education of Liaoning Province