1. Plasma Protein Biomarkers Associated with Higher Ovarian Cancer Risk in BRCA1/2 Carriers
- Author
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Kyunggon Kim, Jung Yoon Ho, Soo Young Hur, Hee-Sung Ahn, Yuyeon Jung, Jiyoung Yu, Sanha Lee, Youn Jin Choi, and Jeonghun Yeom
- Subjects
0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,endocrine system diseases ,medicine.medical_treatment ,proteome ,Population ,Disease ,Proteomics ,Gastroenterology ,Article ,03 medical and health sciences ,0302 clinical medicine ,BRCA1/2 ,Internal medicine ,medicine ,Liquid biopsy ,LC-MS/MS ,skin and connective tissue diseases ,education ,RC254-282 ,plasma ,education.field_of_study ,liquid biopsy ,business.industry ,Oophorectomy ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Blood proteins ,030104 developmental biology ,ovarian cancer ,Oncology ,030220 oncology & carcinogenesis ,Biomarker (medicine) ,biomarker ,ELISA ,Ovarian cancer ,business - Abstract
Ovarian cancer (OC) is the most lethal gynecologic malignancy and in-time diagnosis is limited because of the absence of effective biomarkers. Germline BRCA1/2 genetic alterations are risk factors for hereditary OC, risk-reducing salpingo-oophorectomy (RRSO) is pursued for disease prevention. However, not all healthy carriers develop the disease. Therefore, identifying predictive markers in the BRCA1/2 carrier population could help improve the identification of candidates for preventive RRSO. In this study, plasma samples from 20 OC patients (10 patients with BRCA1/2 wild type (wt) and 10 with the BRCA1/2 variant (var)) and 20 normal subjects (10 subjects with BRCA1/2wt and 10 with BRCA1/2var) were analyzed for potential biomarkers of hereditary OC. We applied a bottom-up proteomics approach, using nano-flow LC-MS to analyze depleted plasma proteome quantitatively, and potential plasma protein markers specific to the BRCA1/2 variant were identified from a comparative statistical analysis of the four groups. We obtained 1505 protein candidates from the 40 subjects, and SPARC and THBS1 were verified by enzyme-linked immunosorbent assay. Plasma SPARC and THBS1 concentrations in healthy BRCA1/2 carriers were found to be lower than in OC patients with BRCA1/2var. If plasma SPARC concentrations increase over 337.35 ng/mL or plasma THBS1 concentrations increase over 65.28 μg/mL in a healthy BRCA1/2 carrier, oophorectomy may be suggested.
- Published
- 2021
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