Molecular features and clinical implications of the heterogeneity in Chinese patients with HER2-low breast cancer.
Molecular features and clinical implications of the heterogeneity in Chinese patients with HER2-low breast cancer.
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DOI：
10.1038/s41467-023-40715-x
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发表时间：
2023-08-22
影响因子：
16.6
通讯作者：
Shao, Zhi-Ming
中科院分区：
文献类型：
--
作者：
Dai, Lei-Jie;Ma, Ding;Xu, Yu-Zheng;Li, Ming;Li, Yu-Wei;Xiao, Yi;Jin, Xi;Wu, Song-Yang;Zhao, Ya-Xin;Wang, Han;Yang, Wen-Tao;Jiang, Yi-Zhou;Shao, Zhi-Ming
HER2-低乳腺癌的分子异质性和独特的特征，特别是在中国人群中，还没有被很好地了解，这限制了它在抗体-药物结合时代的精确治疗。为了解决这一问题，我们建立了434名HER2低乳腺癌患者(433名女性和1名男性)的队列，并整合了基因组、转录组、蛋白质组和代谢组学数据。在这个队列中，在激素受体阴性亚组中，HER2低的肿瘤与HER2-0的肿瘤更有区别。在HER2-Low肿瘤中，激素受体阴性的亚组也存在显著的患者间异质性：基底样瘤类似HER2-0疾病，非基底样HER2-Low肿瘤模仿HER2阳性疾病。这些非基底样低HER2肿瘤富含HER2富集型和管腔雄激素受体亚型，其特征是PIK3CA突变、FGFR4/PTK6/ERBB4过表达和脂代谢激活。在激素受体阳性的肿瘤中，HER2低的肿瘤比HER2-0的肿瘤在17q峰的丢失/缺失更少。在这项工作中，我们揭示了HER2-低乳腺癌的异质性，并强调有必要对激素受体状态和分子亚型进行更精确的分层。HER2-低乳腺癌最近被定义为对新型抗体-药物结合物敏感的潜在亚型。在这里，作者分析了434名HER2-Low患者的多组学队列，发现与其他亚型相比，该亚型的分子状态发生了变化，并且该亚型中患者之间的异质性。
The molecular heterogeneity and distinct features of HER2-low breast cancers, particularly in the Chinese population, are not well understood, limiting its precise management in the era of antibody‒drug conjugates. To address this issue, we established a cohort of 434 Chinese patients with HER2-low breast cancer (433 female and one male) and integrated genomic, transcriptomic, proteomic, and metabolomic profiling data. In this cohort, HER2-low tumors are more distinguished from HER2-0 tumors in the hormone receptor–negative subgroup. Within HER2-low tumors, significant interpatient heterogeneity also exists in the hormone receptor–negative subgroup: basal-like tumors resemble HER2-0 disease, and non-basal-like HER2-low tumors mimic HER2-positive disease. These non-basal-like HER2-low tumors are enriched in the HER2-enriched subtype and the luminal androgen receptor subtype and feature PIK3CA mutation, FGFR4/PTK6/ERBB4 overexpression and lipid metabolism activation. Among hormone receptor–positive tumors, HER2-low tumors show less loss/deletion in 17q peaks than HER2-0 tumors. In this work, we reveal the heterogeneity of HER2-low breast cancers and emphasize the need for more precise stratification regarding hormone receptor status and molecular subtype. HER2-low breast cancer has recently been defined as a potential subtype for sensitivity to novel antibody-drug conjugates. Here, the authors analyse a multiomics cohort of 434 HER2-low patients and find an altered molecular status compared to other subtypes and the interpatient heterogeneity within this subtype.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
三阴性乳腺癌的基因组和转录组景观：亚型和治疗策略
影响因子：
50.3
作者：
Jiang, Yi-Zhou;Ma, Ding;Shao, Zhi-Ming
通讯作者：
Shao, Zhi-Ming
影响因子：
28.2
作者：
Birkbak NJ;Wang ZC;Kim JY;Eklund AC;Li Q;Tian R;Bowman-Colin C;Li Y;Greene-Colozzi A;Iglehart JD;Tung N;Ryan PD;Garber JE;Silver DP;Szallasi Z;Richardson AL
通讯作者：
Richardson AL
影响因子：
37.3
作者：
Du Z;Lovly CM
通讯作者：
Lovly CM
影响因子：
2.7
作者：
Lin，Chun-Lin;Tan，Xi;Huang，Tim H. -M.
通讯作者：
Huang，Tim H. -M.