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Proteogenomic characterization reveals tumorigenesis and progression of lung cancer manifested as subsolid nodules

Author

Listed:
  • Hang Su

    (Tongji University School of Medicine)

  • Li Chen

    (Tongji University School of Medicine
    Tongji University School of Medicine)

  • Jun Wu

    (East China Normal University)

  • Zhongyi Cheng

    (Jingjie PTM BioLab (Hangzhou). Co. Inc)

  • Jing Li

    (Second Military Medical University)

  • Yijiu Ren

    (Tongji University School of Medicine)

  • Junfang Xu

    (Tongji University School of Medicine
    Tongji University School of Medicine)

  • Yifang Dang

    (Tongji University School of Medicine
    Tongji University School of Medicine)

  • Mengge Zheng

    (Tongji University School of Medicine
    Tongji University School of Medicine)

  • Yajuan Cao

    (Tongji University School of Medicine
    Tongji University School of Medicine)

  • Jiani Gao

    (Tongji University School of Medicine)

  • Chenyang Dai

    (Tongji University School of Medicine)

  • Xuefei Hu

    (Tongji University School of Medicine)

  • Huikang Xie

    (Tongji University School of Medicine)

  • Jianxia Chen

    (Tongji University School of Medicine)

  • Tao Luo

    (Jingjie PTM BioLab (Hangzhou). Co. Inc)

  • Jun Zhu

    (Jingjie PTM BioLab (Hangzhou). Co. Inc)

  • Chunyan Wu

    (Tongji University School of Medicine)

  • Wei Sha

    (Tongji University School of Medicine)

  • Chang Chen

    (Tongji University School of Medicine)

  • Haipeng Liu

    (Tongji University School of Medicine
    Tongji University School of Medicine)

Abstract

Lung adenocarcinoma (LUAD) radiologically displayed as subsolid nodules (SSNs) is prevalent. Nevertheless, the precise clinical management of SSNs necessitates a profound understanding of their tumorigenesis and progression. Here, we analyze 66 LUAD displayed as SSNs covering 3 histological stages including adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA) and invasive adenocarcinoma (IAC) by incorporating genomics, proteomics, phosphoproteomics and glycoproteomics. Intriguingly, cholesterol metabolism is aberrantly regulated in the preneoplastic AIS stage. Importantly, target ablation of proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes the initiation of LUAD. Furthermore, sustained endoplasmic reticulum stress is demonstrated to be a hallmark and a reliable biomarker of AIS progression to IAC. Consistently, target promotion of ER stress profoundly retards LUAD progression. Our study provides comprehensive proteogenomic landscape of SSNs, sheds lights on the tumorigenesis and progression of SSNs and suggests preventive and therapeutic strategies for LUAD.

Suggested Citation

  • Hang Su & Li Chen & Jun Wu & Zhongyi Cheng & Jing Li & Yijiu Ren & Junfang Xu & Yifang Dang & Mengge Zheng & Yajuan Cao & Jiani Gao & Chenyang Dai & Xuefei Hu & Huikang Xie & Jianxia Chen & Tao Luo & , 2025. "Proteogenomic characterization reveals tumorigenesis and progression of lung cancer manifested as subsolid nodules," Nature Communications, Nature, vol. 16(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57364-x
    DOI: 10.1038/s41467-025-57364-x
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