中国人群乳腺癌多基因组综合分析揭示了患者分层和治疗弱点。

IF 23.5 1区 医学 Q1 ONCOLOGY Nature cancer Pub Date : 2024-02-12 DOI:10.1038/s43018-024-00725-0
Yi-Zhou Jiang, Ding Ma, Xi Jin, Yi Xiao, Ying Yu, Jinxiu Shi, Yi-Fan Zhou, Tong Fu, Cai-Jin Lin, Lei-Jie Dai, Cheng-Lin Liu, Shen Zhao, Guan-Hua Su, Wanwan Hou, Yaqing Liu, Qingwang Chen, Jingcheng Yang, Naixin Zhang, Wen-Juan Zhang, Wei Liu, Weigang Ge, Wen-Tao Yang, Chao You, Yajia Gu, Virginia Kaklamani, François Bertucci, Claire Verschraegen, Anneleen Daemen, Nakul M. Shah, Ting Wang, Tiannan Guo, Leming Shi, Charles M. Perou, Yuanting Zheng, Wei Huang, Zhi-Ming Shao
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引用次数: 0

摘要

分子图谱分析为乳腺癌的精准治疗提供了指导;然而,在公开的大规模研究中,亚洲患者的代表性不足。我们建立了一个包含 773 名中国乳腺癌患者的综合多组学队列,系统分析了他们的基因组、转录组、蛋白质组、代谢组、放射组和数字病理特征。我们在这里发现,与白人乳腺癌患者相比,亚洲人有更多可靶向的AKT1突变。综合分析表明,在中国的HR+HER2+队列中,HER2富集亚型的比例更高,相应地ERBB2扩增更频繁,HER2蛋白丰度更高,因此这些人需要接受抗HER2治疗。此外,全面的代谢组学和蛋白质组学分析揭示了铁突变是基底样肿瘤的潜在治疗靶点。通过整合临床、转录组学、代谢组学、放射组学和病理学特征,可以有效地将患者分为具有不同复发风险的组别。我们的研究为了解亚洲人乳腺癌的生物学特性和祖先特异性提供了公共资源和新见解,为进一步的精准治疗方法提供了潜力。
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Integrated multiomic profiling of breast cancer in the Chinese population reveals patient stratification and therapeutic vulnerabilities
Molecular profiling guides precision treatment of breast cancer; however, Asian patients are underrepresented in publicly available large-scale studies. We established a comprehensive multiomics cohort of 773 Chinese patients with breast cancer and systematically analyzed their genomic, transcriptomic, proteomic, metabolomic, radiomic and digital pathology characteristics. Here we show that compared to breast cancers in white individuals, Asian individuals had more targetable AKT1 mutations. Integrated analysis revealed a higher proportion of HER2-enriched subtype and correspondingly more frequent ERBB2 amplification and higher HER2 protein abundance in the Chinese HR+HER2+ cohort, stressing anti-HER2 therapy for these individuals. Furthermore, comprehensive metabolomic and proteomic analyses revealed ferroptosis as a potential therapeutic target for basal-like tumors. The integration of clinical, transcriptomic, metabolomic, radiomic and pathological features allowed for efficient stratification of patients into groups with varying recurrence risks. Our study provides a public resource and new insights into the biology and ancestry specificity of breast cancer in the Asian population, offering potential for further precision treatment approaches. Shao and colleagues present a multiomic analysis of breast tumor samples from Chinese patients, consisting of genomic, transcriptomic, proteomic, metabolomic, radiomic and digital pathology data.
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来源期刊
Nature cancer
Nature cancer Medicine-Oncology
CiteScore
31.10
自引率
1.80%
发文量
129
期刊介绍: Cancer is a devastating disease responsible for millions of deaths worldwide. However, many of these deaths could be prevented with improved prevention and treatment strategies. To achieve this, it is crucial to focus on accurate diagnosis, effective treatment methods, and understanding the socioeconomic factors that influence cancer rates. Nature Cancer aims to serve as a unique platform for sharing the latest advancements in cancer research across various scientific fields, encompassing life sciences, physical sciences, applied sciences, and social sciences. The journal is particularly interested in fundamental research that enhances our understanding of tumor development and progression, as well as research that translates this knowledge into clinical applications through innovative diagnostic and therapeutic approaches. Additionally, Nature Cancer welcomes clinical studies that inform cancer diagnosis, treatment, and prevention, along with contributions exploring the societal impact of cancer on a global scale. In addition to publishing original research, Nature Cancer will feature Comments, Reviews, News & Views, Features, and Correspondence that hold significant value for the diverse field of cancer research.
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