DNA-repair ERCC1 Gene Polymorphisms in Epithelial Ovarian Cancer and Relation to Platinum Resistance and Survival

Abstract Purpose One major reason of the high mortality of epithelial ovarian cancer (EOC) is due to platinum-based chemotherapy resistance. Aberrant DNA methylation may be a potential mechanism underlying the development of platinum resistance in EOC. The purpose of this study is to discover potential aberrant DNA methylation that contributes to drug resistance. Methods By initially screening of 16 platinum-sensitive/resistant samples from EOC patients with reduced representation bisulfite sequencing (RRBS), the upstream region of the hMSH2 gene was discovered hypermethylated in the platinum-resistant group. The effect of hMSH2 methylation on the cellular response to cisplatin was explored by demethylation and knockdown assays in ovarian cancer cell line A2780. Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry was employed to examine the methylation levels of hMSH2 upstream region in additional 40 EOC patient samples. RT-qPCR and IHC assay was used to detect the hMSH2 mRNA and protein expression in extended 150 patients. Results RRBS assay discovered an upstream region from − 1193 to − 1125 of hMSH2 was significant hypermethylated in resistant EOC patients (P = 1.06 × 10−14). In vitro analysis demonstrated that global demethylation increased cisplatin sensitivity along with a higher expression of the hMSH2 mRNA and protein. Knockdown hMSH2 reduced the cell sensitivity to cisplatin. MALDI-TOF mass spectrometry assay validated the strong association of hypermethylation of hMSH2 upstream region with platinum resistance. Spearman’s correlation analysis revealed a significantly negative connection between methylation level of hMSH2 upstream region and its expression. The Kaplan-Meier analyses showed the high methylation of hMSH2 promoter region, and its low expressions are associated with worse survival. In multivariable models, hMSH2 low expression was an independent factor predicting poor outcome (P = 0.03, HR = 1.91, 95%CI = 1.85–2.31). Conclusion The hypermethylation of hMSH2 upstream region is associated with platinum resistant in EOC, and low expression of hMSH2 may be an index for the poor prognosis.

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Rs3802278 in 3’-UTR of SULF1 associated with platinum resistance and survival in Chinese epithelial ovarian cancer patients

Journal of Chemotherapy ◽

10.1080/1120009x.2021.1913702 ◽

2021 ◽

pp. 1-6

Author(s):

Feiyue Zeng ◽

Yujie Liu ◽

Qianying Ouyang ◽

Zeen Sun ◽

Keqiang Zhang ◽

...

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Cancer Patients ◽

Platinum Resistance

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SERPINB3 in the Chicken Model of Ovarian Cancer: A Prognostic Factor for Platinum Resistance and Survival in Patients with Epithelial Ovarian Cancer

PLoS ONE ◽

10.1371/journal.pone.0049869 ◽

2012 ◽

Vol 7 (11) ◽

pp. e49869 ◽

Cited By ~ 29

Author(s):

Whasun Lim ◽

Hee Seung Kim ◽

Wooyoung Jeong ◽

Suzie E. Ahn ◽

Jinyoung Kim ◽

...

Keyword(s):

Ovarian Cancer ◽

Prognostic Factor ◽

Epithelial Ovarian Cancer ◽

Platinum Resistance ◽

Chicken Model

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Genetic Association of Interleukin-31 Gene Polymorphisms with Epithelial Ovarian Cancer in Chinese Population

Disease Markers ◽

10.1155/2018/3503858 ◽

2018 ◽

Vol 2018 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Chenlu Liu ◽

Yanyun Wang ◽

Huizi Song ◽

Qin Li ◽

Yan Zhang ◽

...

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Therapeutic Target ◽

Gene Polymorphisms ◽

Chinese Population ◽

Clinical Characteristics ◽

Chinese Women ◽

Healthy Individuals ◽

Potential Therapeutic Target ◽

Kaplan Meier

Roles of interleukin-31 (IL-31) in the development and progression of human epithelial ovarian cancer are largely unknown. Studies report that the polymorphisms, rs7977932 C>G and rs4758680 C>A in IL-31, affect the expression level of IL-31. In the present study, we examined 412 patients with epithelial ovarian cancer and 428 healthy individuals to explore whether these polymorphisms are associated with the epithelial ovarian cancer in Chinese women. The genotype of the polymorphisms in each individual was identified. The associations of the polymorphisms with patients’ clinical characteristics and outcomes were evaluated. For rs7977932, the frequency of the CG/GG was significantly decreased in patients with epithelial ovarian cancer. However, the frequency of the rs4758680 CA/AA was significantly increased in those patients. Moreover, the frequency of rs7977932 CG/GG genotype was significantly higher in patients with less advanced FIGO stages. Kaplan-Meier curve showed that patients with CG/GG genotypes of rs7977932 had a decreased risk for recurrence compared to those with CC genotype. Our findings suggested that rs7977932 and rs4758680 of IL-31 may be associated with the development and progression of the epithelial ovarian cancer in the Chinese population. IL-31, therefore, may be a potential therapeutic target for the development of drugs to treat the disease.

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