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
{"title":"蛋白质基因组学特征显示肺癌的肿瘤发生和进展表现为实下结节","authors":"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","doi":"10.1038/s41467-025-57364-x","DOIUrl":null,"url":null,"abstract":"<p>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.</p>","PeriodicalId":19066,"journal":{"name":"Nature Communications","volume":"4 1","pages":""},"PeriodicalIF":15.7000,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Proteogenomic characterization reveals tumorigenesis and progression of lung cancer manifested as subsolid nodules\",\"authors\":\"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\",\"doi\":\"10.1038/s41467-025-57364-x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>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.</p>\",\"PeriodicalId\":19066,\"journal\":{\"name\":\"Nature Communications\",\"volume\":\"4 1\",\"pages\":\"\"},\"PeriodicalIF\":15.7000,\"publicationDate\":\"2025-03-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Nature Communications\",\"FirstCategoryId\":\"103\",\"ListUrlMain\":\"https://doi.org/10.1038/s41467-025-57364-x\",\"RegionNum\":1,\"RegionCategory\":\"综合性期刊\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MULTIDISCIPLINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nature Communications","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1038/s41467-025-57364-x","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
引用次数: 0
摘要
肺腺癌（LUAD）放射学表现为实下结节（ssn）是普遍存在的。然而，对ssn的精确临床管理需要对其肿瘤发生和进展有深刻的了解。本文采用基因组学、蛋白质组学、磷酸化蛋白质组学和糖蛋白质组学等方法，对66例LUAD进行了ssn分析，涵盖原位腺癌（AIS）、微创腺癌（MIA）和侵袭性腺癌（IAC） 3个组织学阶段。有趣的是，胆固醇代谢在肿瘤前AIS阶段异常调节。重要的是，蛋白转化酶subtilisin/ keexin type 9 （PCSK9）的靶向消融可促进LUAD的启动。此外，持续的内质网应激被证明是AIS进展为IAC的一个标志和可靠的生物标志物。与此一致的是，内质网应激的靶标促进深刻地延缓了LUAD的进展。我们的研究提供了ssn的全面蛋白质基因组图谱，揭示了ssn的肿瘤发生和进展，并提出了LUAD的预防和治疗策略。
Proteogenomic characterization reveals tumorigenesis and progression of lung cancer manifested as subsolid nodules
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.
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.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
