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| Expression of BRCA1, BRCA2, RAD51 and FANCD2 in ovarian cancer tissues and correlation with clinicopathological characteristics |
| LIU Lanlan1， WANG Zhixin2， YUAN Sirui2， SHI Chunyan3， LU Ziwen2， HU Xing3， LIU Hanqing2， TU Zhigang1#br# |
(1. Institute of Life Sciences, Jiangsu University, Zhenjiang Jiangsu 212013; 2. School of Pharmacy, Jiangsu University, Zhenjiang Jiangsu 212013; 3. Department of Gynecology, Affiliated Hospital of Jiangsu University, Zhenjiang Jiangsu 212001, China)
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Abstract Objective: To explore the protein expression of homologous recombination repair genes for DNA doublestrand breaks, such as breast cancer susceptibility protein 1 (BRCA1), breast cancer susceptibility protein 2 (BRCA2), DNA repair protein RAD51 and Fanconi anemia D2 protein (FANCD2), in ovarian cancer tissues and correlation with clinicopathological characteristics. Methods: Paraffin sections of 84 cases of primary epithelial ovarian cancer (EOC) and 6 cases of normal ovarian tissues were collected, and the levels of protein expression of BRCA1, BRCA2, RAD51, and FANCD2 were detected by immunohistochemistry. The expression of the above four proteins in the EOC tissues and the correlation between the proteins in the cancer genome atlas (TCGA) database through GEPIA. Ualcan analyzed the relationship between the expression of the four proteins and the clinicopathological characteristics of EOC in the TCGA database. Results: Immunohistochemical assays revealed that BRCA2, FANCD2 and RAD51 were highly expressed in EOC specimens rather than in normal tissues (all P<0.05). According to the analyses of TCGA database by GEPIA, the mRNA expression of BRCA1, BRCA2, RAD51 and FANCD2 increased in EOC tissues. The expression levels of 4 proteins have a significant positive correlation between each other. According to the results of TCGA database by Ualcan analysis, the mRNA expression of BRCA1 was significantly higher in patients over 41 years of age; expression of these four genes were higher in tumors above grade 2 and the mRNA expression of RAD51 in grade 3 tumors was significantly higher than that in grade 2 tumors; the mRNA expression of FANCD2 in African American was significantly higher than that in Caucasian; the mRNA expression of BRCA1, RAD51, and FANCD2 in TP53mutant tumors was significantly higher than their expression in nonmutant tumors. Conclusion: The expression of BRCA2, FANCD2 and RAD51 was significantly increased in tumor tissues of EOC, and may potentially be candidate biomarkers for diagnosis and treatment of ovarian cancer.
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Received: 28 January 2021
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［1］Torre LA, Trabert B, DeSantis CE, et al. Ovarian cancer statistics［J］. CA Cancer J Clin, 2018, 68(4): 284-296.
［2］Lee JM, Minasian L, Kohn EC. New strategies in ovarian cancer treatment［J］. Cancer, 2019, 125(Suppl 24): 4623-4629.
［3］Haunschild CE, Tewari KS. Bevacizumab use in the frontline, maintenance and recurrent settings for ovarian cancer［J］. Future Oncol, 2020, 16(7): 225-246.
［4］Arora S, Balasubramaniam S, Zhang H, et al. FDA approval summary: Olaparib monotherapy or in combination with bevacizumab for the maintenance treatment of patients with advanced ovarian cancer［J］. Oncologist, 2021, 26(1): e164-e172.
［5］Boussios S, Abson C, Moschetta M, et al. Poly (ADPribose)polymerase inhibitors: talazoparib in ovarian cancer and beyond［J］. Drugs R D, 2020, 20(2): 55-73.
［6］Boussios S, Moschetta M, Karihtala P, et al. Development of new poly(ADPribose) polymerase (PARP) inhibitors in ovarian cancer: Quo Vadis?［J］. Ann Transl Med, 2020, 8(24): 1706.
［7］Colombo I, Lheureux S, Oza AM. Rucaparib: a novel PARP inhibitor for BRCA advanced ovarian cancer［J］. Drug Des Devel Ther, 2018, 12: 605-617.
［8］Mouw KW, Goldberg MS, Konstantinopoulos PA, et al. DNA damage and repair biomarkers of immunotherapy response［J］. Cancer Discov, 2017, 7(7): 675-693.
［9］Liang F, Miller AS, Tang C, et al. The DNAbinding activity of USP1associated factor 1 is required for efficient RAD51mediated homologous DNA pairing and homologydirected DNA repair［J］. J Biol Chem, 2020, 295(24): 8186-8194.
［10］von Nicolai C, Ehlén , Martin C, et al. A second DNA binding site in human BRCA2 promotes homologous recombination［J］. Nat Commun, 2016, 7: 12813.
［11］李玫瑜，李坚，陈康．抑制肺鳞癌细胞FANCM和USP1基因对顺铂的增敏效应［J］．江苏大学学报（医学版），2016, 26(2): 147-153.
［12］Shen Y, Ruan L, Lian C, et al. Discovery of HBEGF binding peptides and their functional characterization in ovarian cancer cell lines［J］. Cell Death Discov, 2019, 5: 82.
［13］Venkitaraman AR. Cancer suppression by the chromosome custodians, BRCA1 and BRCA2［J］. Science, 2014, 343(6178): 1470-1475.
［14］Zhao W, Steinfeld JB, Liang F, et al. BRCA1BARD1 promotes RAD51mediated homologous DNA pairing［J］. Nature, 2017, 550(7676): 360-365.
［15］MoesSosnowska J, Rzepecka IK, Chodzynska J, et al. Clinical importance of FANCD2, BRIP1, BRCA1, BRCA2 and FANCF expression in ovarian carcinomas［J］. Cancer Biol Ther, 2019, 20(6): 843-854.
［16］Taron M, Rosell R, Felip E, et al. BRCA1 mRNA expression levels as an indicator of chemoresistance in lung cancer［J］. Hum Mol Genet, 2004, 13(20): 2443-2449.
［17］Egawa C, Miyoshi Y, Takamura Y, et al. Decreased expression of BRCA2 mRNA predicts favorable response to docetaxel in breast cancer［J］. Int J Cancer, 2001, 95(4): 255-259.
［18］Lee JH, Bae AN, Jung AS. Clinicopathological and prognostic characteristics of RAD51 in colorectal cancer［J］. Medicina (Kaunas), 2020, 56(2): 48.
［19］MoesSosnowska J, Rzepecka IK, Chodzynska J, et al. Clinical importance of FANCD2, BRIP1, BRCA1, BRCA2 and FANCF expression in ovarian carcinomas［J］. Cancer Biol Ther, 2019, 20(6): 843-854.
［20］Chartron E, Theillet C, Guiu S, et al. Targeting homologous repair deficiency in breast and ovarian cancers: Biological pathways, preclinical and clinical data［J］. Crit Rev Oncol Hematol, 2019, 133: 58-73.
［21］Sugino K, Tamura R, Nakaoka H, et al. Germline and somatic mutations of homologous recombinationassociated genes in Japanese ovarian cancer patients［J］. Sci Rep, 2019, 9(1): 17808.
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