TY - JOUR
T1 - Proteogenomic characterization reveals tumorigenesis and progression of lung cancer manifested as subsolid nodules
AU - Su, Hang
AU - Chen, Li
AU - Wu, Jun
AU - Cheng, Zhongyi
AU - Li, Jing
AU - Ren, Yijiu
AU - Xu, Junfang
AU - Dang, Yifang
AU - Zheng, Mengge
AU - Cao, Yajuan
AU - Gao, Jiani
AU - Dai, Chenyang
AU - Hu, Xuefei
AU - Xie, Huikang
AU - Chen, Jianxia
AU - Luo, Tao
AU - Zhu, Jun
AU - Wu, Chunyan
AU - Sha, Wei
AU - Chen, Chang
AU - Liu, Haipeng
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/12
Y1 - 2025/12
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/105000059666
U2 - 10.1038/s41467-025-57364-x
DO - 10.1038/s41467-025-57364-x
M3 - 文章
C2 - 40069142
AN - SCOPUS:105000059666
SN - 2041-1723
VL - 16
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 2414
ER -
可持续发展目标 3 良好健康与福祉