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<p>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 <i>ERBB2</i> mutations and <i>ALK</i>-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 <i>ERBB2</i> 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年2月26日

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  • 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,
  • Xueying Yang

摘要

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.