Integrated multiomic profiling of breast cancer in the Chinese population reveals patient stratification and therapeutic vulnerabilities

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 LiuWeigang 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

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

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.

Original languageEnglish
JournalNature Cancer
DOIs
StateAccepted/In press - 2024

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