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Surfaceome profiling enables isolation of cancer-specific exosomal cargo in liquid biopsies from pancreatic cancer patients.
Castillo, J; Bernard, V; San Lucas, F A; Allenson, K; Capello, M; Kim, D U; Gascoyne, P; Mulu, F C; Stephens, B M; Huang, J; Wang, H; Momin, A A; Jacamo, R O; Katz, M; Wolff, R; Javle, M; Varadhachary, G; Wistuba, I I; Hanash, S; Maitra, A; Alvarez, H.
Afiliación
  • Castillo J; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, USA.
  • Bernard V; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, USA.
  • San Lucas FA; The University of Texas MD Anderson Cancer UTHealth Graduate School of Biomedical Sciences, Houston, USA.
  • Allenson K; Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, USA.
  • Capello M; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
  • Kim DU; Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, USA.
  • Gascoyne P; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, USA.
  • Mulu FC; ContinuumDx, Houston, USA.
  • Stephens BM; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, USA.
  • Huang J; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, USA.
  • Wang H; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, USA.
  • Momin AA; McCombs Institute for the Early Detection and Treatment of Cancer, The University of Texas MD Anderson Cancer Center, Houston, USA.
  • Jacamo RO; McCombs Institute for the Early Detection and Treatment of Cancer, The University of Texas MD Anderson Cancer Center, Houston, USA.
  • Katz M; Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, USA.
  • Wolff R; Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
  • Javle M; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
  • Varadhachary G; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
  • Wistuba II; Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
  • Hanash S; Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, USA.
  • Maitra A; Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, USA.
  • Alvarez H; Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, USA.
Ann Oncol ; 29(1): 223-229, 2018 01 01.
Article en En | MEDLINE | ID: mdl-29045505
Background: Detection of circulating tumor DNA can be limited due to their relative scarcity in circulation, particularly while patients are actively undergoing therapy. Exosomes provide a vehicle through which cancer-specific material can be enriched from the compendium of circulating non-neoplastic tissue-derived nucleic acids. We carried out a comprehensive profiling of the pancreatic ductal adenocarcinoma (PDAC) exosomal 'surfaceome' in order to identify surface proteins that will render liquid biopsies amenable to cancer-derived exosome enrichment for downstream molecular profiling. Patients and methods: Surface exosomal proteins were profiled in 13 human PDAC and 2 non-neoplastic cell lines by liquid chromatography-mass spectrometry. A total of 173 prospectively collected blood samples from 103 PDAC patients underwent exosome isolation. Droplet digital PCR was used on 74 patients (136 total exosome samples) to determine baseline KRAS mutation call rates while patients were on therapy. PDAC-specific exosome capture was then carried out on additional 29 patients (37 samples) using an antibody cocktail directed against selected proteins, followed by droplet digital PCR analysis. Exosomal DNA in a PDAC patient resistant to therapy were profiled using a molecular barcoded, targeted sequencing panel to determine the utility of enriched nucleic acid material for comprehensive molecular analysis. Results: Proteomic analysis of the exosome 'surfaceome' revealed multiple PDAC-specific biomarker candidates: CLDN4, EPCAM, CD151, LGALS3BP, HIST2H2BE, and HIST2H2BF. KRAS mutations in total exosomes were detected in 44.1% of patients undergoing active therapy compared with 73.0% following exosome capture using the selected biomarkers. Enrichment of exosomal cargo was amenable to molecular profiling, elucidating a putative mechanism of resistance to PARP inhibitor therapy in a patient harboring a BRCA2 mutation. Conclusion: Exosomes provide unique opportunities in the context of liquid biopsies for enrichment of tumor-specific material in circulation. We present a comprehensive surfaceome characterization of PDAC exosomes which allows for capture and molecular profiling of tumor-derived DNA.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Carcinoma Ductal Pancreático / Exosomas / Proteínas de Neoplasias Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Ann Oncol Asunto de la revista: NEOPLASIAS Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Neoplasias Pancreáticas / Carcinoma Ductal Pancreático / Exosomas / Proteínas de Neoplasias Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Ann Oncol Asunto de la revista: NEOPLASIAS Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos