2. Academic Validation
  3. Proteomic Profiling of Serum Extracellular Vesicles Identifies Diagnostic Signatures and Therapeutic Targets in Breast Cancer

Proteomic Profiling of Serum Extracellular Vesicles Identifies Diagnostic Signatures and Therapeutic Targets in Breast Cancer

  • Cancer Res. 2024 Jun 20. doi: 10.1158/0008-5472.CAN-23-3998.
Ganfei Xu 1,  Rui Huang 2,  Reziya Wumaier 2,  Jiacheng Lyu 1,  Minjing Huang 3,  Yaya Zhang 4,  Qingjian Chen 2,  Wenting Liu 5,  Mengyu Tao 6,  Junjian Li 7,  Zhonghua Tao 2,  Bo Yu 2,  Erxiang Xu 8,  Lingfeng Wang 8,  Guoying Yu 9,  Olivier Gires 10,  Lei Zhou 11,  Wei Zhu 12,  Chen Ding 1,  Hongxia Wang 2
Affiliations

Affiliations

  • 1 Fudan University, Shanghai, China.
  • 2 Fudan University Shanghai Cancer Center, Shanghai, China.
  • 3 Fudan University, shanghai, China.
  • 4 Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • 5 Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China.
  • 6 Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, China, China.
  • 7 Shanghai General Hospital, Shanghai, China.
  • 8 910th Hospital of the People's Liberation Army Joint Logistics and Security ForcesFudan University Shanghai Cancer Center, Fijian, China.
  • 9 Henan Normal University, China.
  • 10 Ludwig-Maximilians-University Munich, Germany, Munich, Germany.
  • 11 The Hong Kong Polytechnic University, Hong Kong, Hong Kong.
  • 12 Zhongshan Hospital Fudan University, China.
PMID: 38900939 DOI: 10.1158/0008-5472.CAN-23-3998
Abstract

Analysis of extracellular vesicles (EVs) is a promising noninvasive liquid biopsy approach for breast Cancer (BC) detection, prognosis, and therapeutic monitoring. A comprehensive understanding of the characteristics and proteomic composition of BC-specific EVs from human samples is required to realize the potential of this strategy. In this study, we applied a mass spectrometry-based, data-independent acquisition (DIA) proteomic approach to characterize human serum EVs derived from patients with BC (n = 126) and healthy donors (HDs, n = 70) in a discovery cohort and validated the findings in five independent cohorts. Examination of the EV proteomes enabled construction of specific EV protein classifiers for diagnosing BC and distinguishing patients with metastatic disease. Of note, TALDO1 was found to be an EV biomarker of distant metastasis of BC. In vitro and in vivo analysis confirmed the role of TALDO1 in stimulating BC invasion and metastasis. Finally, high-throughput molecular docking and virtual screening of a library consisting of 271,380 small molecules identified a potent TALDO1 allosteric inhibitor, AO-022, which could inhibit BC migration in vitro and tumor progression in vivo. Together, this work elucidates the proteomic alterations in the serum EVs of BC patients to guide development of improved diagnosis, monitoring, and treatment strategies.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-159130
    TALDO1 Inhibitor