美国麻省理工学院和哈佛大学的布罗德研究所Gilbert S. Omenn研究小组提出了不同种族和暴露的肺腺癌的综合分析。2025年7月31日，国际知名学术期刊《癌细胞》发表了这一成果。

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。结合蛋白质组学和翻译后修饰与基因组学的蛋白质基因组学研究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阻力促进了这一毁灭性疾病的精确管理策略的目标。

附：英文原文

Title: Integrative analysis of lung adenocarcinoma across diverse ethnicities and exposures

Author: 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, M. Harry Kane, Ashley Wolfe, Miloni Kinarivala, Wenke Liu, Shankara Anand, Mong-Wei Lin, Moe Haines, Erik J. Bergstrom, Grant Hussey, Ginny Xiaohe Li, Deepak C. Mani, Hao Fang, Eric J. Jaehnig, Hasmik Keshishian, Brecca Miller, Kang-Yi Su, Yi-Jing Hsiao, Hsao-Hsun Hsu, Min-Shu Hsieh, Kuo-Hsuan Hsu, Alexi Monovoukas, Simone Gohsman, John R. Thorup, Yamei Deng, Yo Akiyama, Eden Deng, Eric Sheng-Wen Chen, Azra Krek, Rodrigo Espinoza, Weiping Ma, Daniel Charytonowicz, Robert Sebra, Jyun-Hong Lin, Yan-Si Chen, Yin-Chen Hsu, Ze-Shiang Lin, Kun-Chieh Chen, Chang-Wei Yeh, Yu-Tai Wang, Alexander J. Lazar, Mehdi Mesri, Eunkyung An, Xu Zhang, Karl R. Clauser, David Feny, Arul M. Chinnaiyan, Bing Zhang, Li Ding, Kelly Ruggles, Chelsea Newton, Hui Zhang, Pei Wang, Galen Hostetter, Gilbert S. Omenn

Issue&Volume: 2025-07-31

Abstract: 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.

DOI: 10.1016/j.ccell.2025.07.011

Source: https://www.cell.com/cancer-cell/abstract/S1535-6108(25)00317-4