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

IF 14.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Nature Communications Pub Date : 2025-03-11 DOI:10.1038/s41467-025-57364-x

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, Jun Zhu, Chunyan Wu, Wei Sha, Chang Chen, Haipeng Liu

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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.

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来源期刊

Nature Communications Biological Science Disciplines-

CiteScore

24.90

自引率

2.40%

发文量

6928

审稿时长

3.7 months

期刊介绍： Nature Communications, an open-access journal, publishes high-quality research spanning all areas of the natural sciences. Papers featured in the journal showcase significant advances relevant to specialists in each respective field. With a 2-year impact factor of 16.6 (2022) and a median time of 8 days from submission to the first editorial decision, Nature Communications is committed to rapid dissemination of research findings. As a multidisciplinary journal, it welcomes contributions from biological, health, physical, chemical, Earth, social, mathematical, applied, and engineering sciences, aiming to highlight important breakthroughs within each domain.