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  3. Proteogenomic Landscape of Breast Ductal Carcinoma Reveals Tumor Progression Characteristics and Therapeutic Targets

Proteogenomic Landscape of Breast Ductal Carcinoma Reveals Tumor Progression Characteristics and Therapeutic Targets

  • Adv Sci (Weinh). 2024 Oct 17:e2401041. doi: 10.1002/advs.202401041.
Ganfei Xu 1,  Juan Yu 1,  Jiacheng Lyu 1,  Mengna Zhan 1,  Jie Xu 1,  Minjing Huang 1,  Rui Zhao 2,  Yan Li 1,  Jiajun Zhu 1,  Jinwen Feng 1,  Subei Tan 1,  Peng Ran 1,  Zhenghua Su 1,  Xinhua Liu 1,  Jianyuan Zhao 2,  Hongwei Zhang 1,  Chen Xu 1,  Jun Chang 1,  Yingyong Hou 1,  Chen Ding 1 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, 200433, China.
  • 2 Institute for Developmental and Regenerative Cardiovascular Medicine, MOE-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China.
  • 3 Departments of Cancer Research Institute, Affiliated Cancer Hospital of Xinjiang Medical University, Xinjiang Key Laboratory of Translational Biomedical Engineering, Urumqi, 830000, P. R. China.
PMID: 39418072 DOI: 10.1002/advs.202401041
Abstract

Multi-omics studies of breast ductal carcinoma (BRDC) have advanced the understanding of the disease's biology and accelerated targeted therapies. However, the temporal order of a series of biological events in the progression of BRDC is still poorly understood. A comprehensive proteogenomic analysis of 224 samples from 168 patients with malignant and benign breast diseases is carried out. Proteogenomic analysis reveals the characteristics of linear multi-step progression of BRDC, such as tumor protein P53 (TP53) mutation-associated Estrogen Receptor 1 (ESR1) overexpression is involved in the transition from ductal hyperplasia (DH) to ductal carcinoma in situ (DCIS). 6q21 amplification-associated nuclear receptor subfamily 3 group C member 1 (NR3C1) overexpression helps DCIS_Pure (pure DCIS, no histologic evidence of invasion) cells avoid immune destruction. The T-cell lymphoma invasion and metastasis 1, Androgen Receptor, and aldo-keto reductase family 1 member C1 (TIAM1-AR-AKR1C1) axis promotes cell invasion and migration in DCIS_adjIDC (DCIS regions of invasive cancers). In addition, AKR1C1 is identified as a potential therapeutic target and demonstrated the inhibitory effect of aspirin and dydrogesterone as its inhibitors on tumor cells. The integrative multi-omics analysis helps to understand the progression of BRDC and provides an opportunity to treat BRDC in different stages.

Keywords

AKR1C1; breast ductal carcinoma; progression; proteogenomics; sterol hormone receptor.

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