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Proteomic Profiling of Serum Extracellular Vesicles Identifies Diagnostic Signatures and Therapeutic Targets in Breast Cancer.
Xu, Ganfei; Huang, Rui; Wumaier, Reziya; Lyu, Jiacheng; Huang, Minjing; Zhang, Yaya; Chen, Qingjian; Liu, Wenting; Tao, Mengyu; Li, Junjian; Tao, Zhonghua; Yu, Bo; Xu, Erxiang; Wang, Lingfeng; Yu, Guoying; Gires, Olivier; Zhou, Lei; Zhu, Wei; Ding, Chen; Wang, Hongxia.
Afiliação
  • Xu G; Department of Medical Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, China.
  • Huang R; Department of Medical Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, China.
  • Wumaier R; Department of Oncology, State Key Laboratory of Systems Medicine for Cancer, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Lyu J; Department of Medical Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, China.
  • Huang M; Department of Oncology, State Key Laboratory of Systems Medicine for Cancer, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Zhang Y; Department of Medical Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, China.
  • Chen Q; Department of Medical Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, China.
  • Liu W; Department of Oncology, State Key Laboratory of Systems Medicine for Cancer, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Tao M; Department of Medical Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, China.
  • Li J; Department of Medical Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, China.
  • Tao Z; Department of Medical Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, China.
  • Yu B; Department of Medical Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, China.
  • Xu E; Department of Medical Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, China.
  • Wang L; Department of Medical Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, State Key Laboratory of Genetic Engineering, School of Life Sciences, Human Phenome Institute, Fudan University, Shanghai, China.
  • Yu G; 910th Hospital of the People's Liberation Army Joint Logistics and Security Forces, Quanzhou, China.
  • Gires O; 910th Hospital of the People's Liberation Army Joint Logistics and Security Forces, Quanzhou, China.
  • Zhou L; State Key Laboratory of Cell Differentiation and Regulation, Henan International Joint Laboratory of Pulmonary Fibrosis, Henan Center for Outstanding Overseas Scientists of Organ Fibrosis, College of Life Science, Henan Normal University, Xinxiang, China.
  • Zhu W; Department of Otorhinolaryngology, LMU University Hospital, LUM Munich, Germany.
  • Ding C; School of Optometry, Department of Applied Biology and Chemical Technology, Research Centre for SHARP Vision, The Hong Kong Polytechnic University; Centre for Eye and Vision Research, Hong Kong, China.
  • Wang H; Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.
Cancer Res ; 84(19): 3267-3285, 2024 Oct 01.
Article em En | MEDLINE | ID: mdl-38900939
ABSTRACT
Analysis of extracellular vesicles (EV) is a promising noninvasive liquid biopsy approach for breast cancer detection, prognosis, and therapeutic monitoring. A comprehensive understanding of the characteristics and proteomic composition of breast cancer-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 proteomic approach to characterize human serum EVs derived from patients with breast cancer (n = 126) and healthy donors (n = 70) in a discovery cohort and validated the findings in five independent cohorts. Examination of the EV proteomes enabled the construction of specific EV protein classifiers for diagnosing breast cancer and distinguishing patients with metastatic disease. Of note, TALDO1 was found to be an EV biomarker of distant metastasis of breast cancer. In vitro and in vivo analysis confirmed the role of TALDO1 in stimulating breast cancer 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 breast cancer migration in vitro and tumor progression in vivo. Together, this work elucidates the proteomic alterations in the serum EVs of breast cancer patients to guide the development of improved diagnosis, monitoring, and treatment strategies.

Significance:

Characterization of the proteomic composition of circulating extracellar vesicles in breast cancer patients identifies signatures for diagnosing primary and metastatic tumors and reveals tumor-promoting cargo that can be targeted to improve outcomes.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Biomarcadores Tumorais / Proteômica / Vesículas Extracelulares Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias da Mama / Biomarcadores Tumorais / Proteômica / Vesículas Extracelulares Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2024 Tipo de documento: Article