title: Clinicopathological values of NBS1 and DNA damage response genes in epithelial ovarian cancers.
abstract: Epithelial ovarian cancers (EOCs) are highly lethal gynecological malignancies with a high recurrence rate. Therefore, developing prognostic markers for recurrence after chemotherapy is crucial for the treatment of ovarian cancers. As ovarian cancers frequently respond to DNA-damaging agents, we assessed the clinicopathological significance of key double-strand DNA break (DSB) repair genes, including BRCA1, BRCA2, BARD1, ATM, RAD51 and NBS1 in EOC cell lines and paraffin-embedded tissue sections from 140 EOC patients treated with cytoreductive surgery, followed by platinum-based chemotherapy. These samples were analyzed for the clinicopathological impact of DSB genes by western blot analysis, immunohistochemistry and quantitative real-time PCR. Of the DSB repair genes, BRCA1, ATM and NBS1, which are involved in the homologous recombination-mediated repair pathway, were related to aggressive parameters in EOC. When survival analysis was performed, NBS1 expression exhibited an association with EOC recurrence. Specifically, increased NBS1 expression was found in 107 out of 140 cases (76.0%) and correlated with advanced stage (P=0.001), high grade (P=0.001) and serous histology (P=0.008). The median recurrence-free survival in patients with positive and negative expression of NBS1 was 30 and 78 months, respectively (P=0.0068). In multivariate analysis, NBS1 was an independent prognostic factor for the recurrence of EOC. Together, these results suggest that NBS1 is a marker of poor prognosis for the recurrence of EOC and is associated with aggressive clinicopathological parameters.
authors.affiliation: Department of Biological Sciences and Institute of Molecular Biology and Genetics, Seoul National University, Seoul, Korea.|Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, Korea.|Department of Obstetrics and Gynecology, Cheil General Hospital, College of Medicine, Dankook University, Seoul, Korea.
authors.forename: Yoo-Kyung
authors.identifier: http://orcid.org/0000-0002-0621-8030
authors.initials: YK
authors.lastname: Lee
authors.affiliation: Department of Obstetrics and Gynecology, Seoul National University Hospital, Seoul, Korea.
authors.forename: Noh-Hyun
authors.initials: NH
authors.lastname: Park
authors.affiliation: Department of Biological Sciences and Institute of Molecular Biology and Genetics, Seoul National University, Seoul, Korea.
authors.forename: Hyunsook
authors.identifier: http://orcid.org/0000-0002-2251-5019
authors.initials: H
authors.lastname: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D000077216:Carcinoma, Ovarian Epithelial; D018797:Cell Cycle Proteins / Q000032:analysis / Q000235:genetics*; D045744:Cell Line, Tumor; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D009687:Nuclear Proteins / Q000032:analysis / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D010053:Ovary / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins