title: [Clinical significance and distribution of BRCA genes mutation in sporadic high grade serous ovarian cancer].
abstract: Objective:To investigate the mutations of BRCA genes in sporadic high grade serous ovarian cancer (HGSOC) and study its clinical significance.Methods:Sixty-eight patients between January 2015 and January 2016 from the Affiliated Cancer Hospital of Zhengzhou University were collected who were based on pathological diagnosis of ovarian cancer and had no reported family history, and all patients firstly hospitalized were untreated in other hospitals before. (1) The BRCA genes were detected by next-generation sequencing (NGS) method. (2) The serum tumor markers included carcinoembryonic antigen (CEA), CA(125), CA(199), and human epididymis protein 4 (HE4) were detected by the chemiluminescence methods, and their correlation was analyzed by Pearson linear correlation. Descriptive statistics and comparisons were performed using two-tailedt-tests, Pearson's chi square test, Fisher's exact tests or logistic regression analysis as appropriate to research the clinicopathologic features associated with BRCA mutations, including age, International Federation of Gynecology and Obstetrics (FIGO) stage, platinum-based chemotherapy sensitivity, distant metastases, serum tumor markers (STM) .Results:(1) Fifteen cases (22%, 15/68) BRCA mutations were identified (BRCA1: 11 cases; BRCA2: 4 cases), and four novel mutations were observed. (2) The levels of CEA, CA(199), and HE4 were lower in BRCA mutations compared to that in control group, while no significant differences were found (P>0.05), but the level of CA(125) was much higher in BRCA mutation group than that in controls (t=-3.536,P=0.003). Further linear regression analysis found that there was a significant linear correlation between CA(125) and HE4 group (r=0.494,P<0.01), and the same correlation as CEA and CA(199) group (r=0.897,P<0.01). (3) Single factor analysis showed that no significant differences were observed in onset age, FIGO stage, distant metastasis, and STM between BRCA(+) and BRCA(-) group (P>0.05), while significant differences were found in CA(125) and sensitivity to platinum-based chemotherapy between the patients with BRCA mutation and wild type (P<0.05). The multiple factors analysis showed that the high level of CA(125) was a independent risk factor of BRCA mutations in sporadic HGSOC (P=0.007).Conclusion:The combination of CA(125) with BRCA have great clinical significance, the mutation of BRCA gene could guild the clinical chemotherapy regiments.
authors.affiliation: Department of Molecular Pathology, the Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450000, China.
authors.forename: W L
authors.initials: WL
authors.lastname: Liu
authors.forename: Z Z
authors.initials: ZZ
authors.lastname: Wang
authors.forename: J Z
authors.initials: JZ
authors.lastname: Zhao
authors.forename: Y Y
authors.initials: YY
authors.lastname: Hou
authors.forename: X X
authors.initials: XX
authors.lastname: Wu
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.forename: B
authors.initials: B
authors.lastname: Dong
authors.forename: T T
authors.initials: TT
authors.lastname: Tong
authors.forename: Y J
authors.initials: YJ
authors.lastname: Guo
mesh_terms: D000328:Adult; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D000077216:Carcinoma, Ovarian Epithelial; D018284:Cystadenocarcinoma, Serous / Q000235:genetics* / Q000473:pathology; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009375:Neoplasms, Glandular and Epithelial; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D011506:Proteins / Q000235:genetics; D000081102:WAP Four-Disulfide Core Domain Protein 2
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D011506:Proteins; D000081102:WAP Four-Disulfide Core Domain Protein 2; C569698:WFDC2 protein, human
keywords: Antineoplastic combined chemotherapy protocols; CA-125 antigen; Cystadenocarcinoma, serous; Genes, BRCA1; Genes, BRCA2; Mutation; Ovarian neoplasms