不同种族和暴露的肺腺癌的综合分析

IF 44.5 1区医学 Q1 CELL BIOLOGY

Cancer Cell Pub Date : 2025-07-31 DOI:10.1016/j.ccell.2025.07.011

Shankha Satpathy, Natalie M. Clark, Yi-Ju Chen, Noshad Hosseini, Ya-Hsuan Chang, Yi Hsiao, Jonathan T. Lei, Francesca Petralia, Jin-Shing Chen, Yifat Geffen, David I. Heiman, Indranil Paul, Hanbyul Cho, Michelle Hollenberg, Giacomo B. Marino, Kuen-Tyng Lin, Rahul Mannan, C. Jackson White, Joe Allen, Shayan C. Avanessian, Zoran Andric

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引用次数: 0

摘要

肺腺癌（LUAD）是一个紧迫的全球健康问题，具有持久的致死率和快速变化的流行病学。蛋白质基因组学研究将蛋白质组学和翻译后修饰与基因组学相结合，可以确定临床层次和致癌机制，但在检查种族、吸烟和环境暴露或性别对这种异质性疾病的影响方面能力不足。本研究对406例不同地理和人口背景的LUAD肿瘤和匹配的正常邻近组织进行了全面的蛋白质基因组学分析，探讨了未被研究的驱动突变的影响、染色体不稳定性的预后作用、免疫信号传导模式、内源性诱变剂和环境致癌物的差异和性别特异性效应，以及具有“晚期样”特征的早期肿瘤的病理生物学。候选的蛋白质生物标志物提出了不稳定的肿瘤与高度碎片化的基因组和致癌物暴露，并提出了LUAD亚型特异性的治疗脆弱性图谱。这些观察结果和相关的数据资源促进了这一毁灭性疾病的精确管理战略的目标。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Integrative analysis of lung adenocarcinoma across diverse ethnicities and exposures

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Integrative analysis of lung adenocarcinoma across diverse ethnicities and exposures

Lung adenocarcinomas (LUAD) are a pressing global health problem with enduring lethality and rapidly shifting epidemiology. Proteogenomic studies integrating proteomics and post-translational modifications with genomics can identify clinical strata and oncogenic mechanisms, but have been underpowered to examine effects of ethnicity, smoking and environmental exposures, or sex on this heterogeneous disease. This comprehensive proteogenomic analysis of LUAD tumors and matched normal adjacent tissues from 406 patients across diverse geographic and demographic backgrounds explores the impact of understudied driver mutations, prognostic role of chromosomal instability, patterns of immune signaling, differential and sex-specific effects of endogenous mutagens and environmental carcinogens, and pathobiology of early-stage tumors with “late-like” characteristics. Candidate protein biomarkers are proposed for unstable tumors with highly fragmented genomes and for carcinogen exposures, and a LUAD subtype-specific atlas of therapeutic vulnerabilities is presented. These observations and the associated data resource advance the objective of precision management strategies for this devastating disease.

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来源期刊

Cancer Cell 医学-肿瘤学

CiteScore

55.20

自引率

1.20%

发文量

179

审稿时长

4-8 weeks

期刊介绍： Cancer Cell is a journal that focuses on promoting major advances in cancer research and oncology. The primary criteria for considering manuscripts are as follows: Major advances: Manuscripts should provide significant advancements in answering important questions related to naturally occurring cancers. Translational research: The journal welcomes translational research, which involves the application of basic scientific findings to human health and clinical practice. Clinical investigations: Cancer Cell is interested in publishing clinical investigations that contribute to establishing new paradigms in the treatment, diagnosis, or prevention of cancers. Insights into cancer biology: The journal values clinical investigations that provide important insights into cancer biology beyond what has been revealed by preclinical studies. Mechanism-based proof-of-principle studies: Cancer Cell encourages the publication of mechanism-based proof-of-principle clinical studies, which demonstrate the feasibility of a specific therapeutic approach or diagnostic test.