Abstract
Objective
To assess the 5′ CpG island methylation of Fanconi anemia, complementation group F (FANCF) gene in epithelial ovarian cancer (EOC) tissues and normal ovarian tissues and to investigate the relationship between FANCF methylation and clinicopathologic features and prognosis of EOC.
Methods
The experiment was performed with 112 EOC tissue samples (case group) and 60 normal ovarian tissues (control group). With methylation-specific polymerase chain reaction (MSP), FANCF methylation status of cases and controls was assessed. And the association between FANCF methylation and the clinicopathological features of EOC was investigated with univariate survival analysis and Cox regression model analysis.
Results
The methylation-positive rate of the case group was significantly higher than that of the control group (P = 0.015). The FANCF promoter methylation rates showed significant differences in the comparisons stratified by age, International Federation of Gynecology and Obstetrics (FIGO) staging, histopathological classification, and lymph node metastasis (all P < .05). Univariate survival analysis showed there were significant differences in mean survival time between the groups based on FIGO staging, histopathological classification, lymph node metastasis, and FANCF methylation (all P < .05). Cox regression model analysis suggested that FIGO staging and FANCF methylation were independent risk factors for EOC prognosis.
Conclusion
CpG island methylation of FANCF gene promoter region is strongly associated with the susceptibility and clinicopathologic features of EOC. The FIGO staging and FANCF methylation are independent risk factors for EOC prognosis.
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References
Chudecka-Glaz AM. ROMA, an algorithm for ovarian cancer. Clin Chim Acta. 2015;440:143–151.
Ross JS, Ali SM, Wang K, et al. Comprehensive genomic profiling of epithelial ovarian cancer by next generation sequencingbased diagnostic assay reveals new routes to targeted therapies. Gynecol Oncol. 2013;130(3):554–559.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.
Lowe KA, Chia VM, Taylor A, et al. An international assessment of ovarian cancer incidence and mortality. Gynecol Oncol. 2013;130(1):107–114.
Sala E, Priest AN, Kataoka M, et al. Apparent diffusion coefficient and vascular signal fraction measurements with magnetic resonance imaging: feasibility in metastatic ovarian cancer at 3 Tesla: technical development. Eur Radiol. 2010;20(2):491–496.
Birkbak NJ, Eklund AC, Li Q, et al. Paradoxical relationship between chromosomal instability and survival outcome in cancer. Cancer Res. 2011;71(10):3447–3452.
D’Andrea AD. Susceptibility pathways in Fanconi’s anemia and breast cancer. N Engl J Med. 2010;362(20):1909–1919.
Zhao L, Li N, Yu JK, et al. RNAi-mediated knockdown of FANCF suppresses cell proliferation, migration, invasion, and drug resistance potential of breast cancer cells. Braz J Med Biol Res. 2014;47(1):24–34.
Litman R, Gupta R, Brosh RM Jr, Cantor SB. BRCA-FA pathway as a target for anti-tumor drugs. Anticancer Agents Med Chem. 2008;8(4):426–430.
Kowal P, Gurtan AM, Stuckert P, D’Andrea AD, Ellenberger T. Structural determinants of human FANCF protein that function in the assembly of a DNA damage signaling complex. J Biol Chem. 2007;282(3):2047–2055.
Vollan HK, Rueda OM, Chin SF, et al. A tumor DNA complex aberration index is an independent predictor of survival in breast and ovarian cancer. Mol Oncol. 2015;9(1):115–127.
Stoepker C, Ameziane N, van der Lelij P, et al. Defects in the fanconi anemia pathway and chromatid cohesion in head and neck cancer. Cancer Res. 2015;75(17):3543–3553.
Guo H, Yan W, Yang Y, Guo M. [Promoter region methylation of DNA damage repair genes in human gastric cancer]. Zhonghua Yi Xue Za Zhi. 2014;94(28):2193–2196.
M PN. World medical association publishes the revised declaration of helsinki. Natl Med J India. 2014;27(1):56.
Committee FO. FIGO staging for gestational trophoblastic neoplasia 2000. FIGO oncology committee. Int J Gynaecol Obstet. 2002;77(3):285–287.
Scully RE, Sobin LH. World Health Organization International Histological Classification of Tumours-Histological Typing of Ovarian Tumours. Springer Verlag, Berlin;1999.
Taniguchi T, Tischkowitz M, Ameziane N, et al. Disruption of the Fanconi anemia-BRCA pathway in cisplatin-sensitive ovarian tumors. Nat Med. 2003;9(5):568–574.
Olopade OI, Wei M. FANCF methylation contributes to chemoselectivity in ovarian cancer. Cancer Cell. 2003;3(5):417–420.
Joo MK, Kim KH, Park JJ, et al. CpG island promoter hypermethylation of Ras association domain family 1A gene contributes to gastric carcinogenesis. Mol Med Rep. 2015;11(4):3039–3046.
Knudson A. Alfred Knudson and his two-hit hypothesis. (Interview by Ezzie Hutchinson). Lancet Oncol. 2001;2(10):642–645.
He M, Sun HG, Hao JY, et al. RNA interference-mediated FANCF silencing sensitizes OVCAR3 ovarian cancer cells to adriamycin through increased adriamycin-induced apoptosis dependent on JNK activation. Oncol Rep. 2013;29(5):1721–1729.
Wang Z, Li M, Lu S, Zhang Y, Wang H. Promoter hypermethylation of FANCF plays an important role in the occurrence of ovarian cancer through disrupting Fanconi anemia-BRCA pathway. Cancer Biol Ther. 2006;5(3):256–260.
Yang HJ, Liu VW, Wang Y, Tsang PC, Ngan HY. Differential DNA methylation profiles in gynecological cancers and correlation with clinico-pathological data. BMC Cancer. 2006;6:212.
Wang Z, Li M, Lu S, Zhang Y, Wang H. Promoter hypermethylation of FANCF plays an important role in the occurrence of ovarian cancer through disrupting Fanconi anemia-BRCA pathway. Cancer Biol Ther. 2006;5(3):256–260.
Lahtz C, Pfeifer GP. Epigenetic changes of DNA repair genes in cancer. J Mol Cell Biol. 2011;3(1):51–58.
Bouffard F, Plourde K, Belanger S, Ouellette G, Labrie Y, Durocher F. Analysis of a FANCE splice isoform in regard to dna repair. J Mol Biol. 2015;427(19):3056–3073.
Narayan G, Arias-Pulido H, Nandula SV, et al. Promoter hypermethylation of FANCF: disruption of Fanconi Anemia-BRCA pathway in cervical cancer. Cancer Res. 2004;64(9):2994–2997.
Dhillon VS, Shahid M, Husain SA. CpG methylation of the FHIT, FANCF, cyclin-D2, BRCA2 and RUNX3 genes in Granulosa cell tumors (GCTs) of ovarian origin. Mol Cancer. 2004;3:33.
Marsit CJ, Liu M, Nelson HH, Posner M, Suzuki M, Kelsey KT. Inactivation of the Fanconi anemia/BRCA pathway in lung and oral cancers: implications for treatment and survival. Oncogene. 2004;23(4):1000–1004.
Lim SL, Smith P, Syed N, et al. Promoter hypermethylation of FANCF and outcome in advanced ovarian cancer. Br J Cancer. 2008;98(8):1452–1456.
Bakker ST, van de Vrugt HJ, Visser JA, et al. Fancf-deficient mice are prone to develop ovarian tumours. J Pathol. 2012;226(1):28–39.
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Ding, JJ., Wang, G., Shi, WX. et al. Promoter Hypermethylation of FANCF and Susceptibility and Prognosis of Epithelial Ovarian Cancer. Reprod. Sci. 23, 24–30 (2016). https://doi.org/10.1177/1933719115612136
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DOI: https://doi.org/10.1177/1933719115612136