J Cancer 2020; 11(23):6850-6860. doi:10.7150/jca.48218

Research Paper

Functional genetic variants of CTNNBIP1 predict platinum treatment response of Chinese epithelial ovarian cancer patients

Haoran Li1,2#, Lihua Chen1,2#, Xiaoxia Tong1,2, Hongji Dai3,4, Tingyan Shi5, Xi Cheng2,6, Menghong Sun7, Kexin Chen3,4, Qingyi Wei1,8,9✉, Mengyun Wang1,2✉

1. Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai, China.
2. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
3. Department of Epidemiology and Biostatistics, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
4. Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China.
5. Ovarian Cancer Program, Division of Gynecologic Oncology, Department of Gynecology and Obstetrics, Fudan University Zhongshan Hospital, Shanghai, China.
6. Department of Gynecological Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
7. Department of Pathology, Tissue Bank, Fudan University Shanghai Cancer Center, Shanghai, China.
8. Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.
9. Department of Population Health Sciences, Duke University School of Medicine, Durham, NC, USA.
#These authors contributed equally to this work.

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Citation:
Li H, Chen L, Tong X, Dai H, Shi T, Cheng X, Sun M, Chen K, Wei Q, Wang M. Functional genetic variants of CTNNBIP1 predict platinum treatment response of Chinese epithelial ovarian cancer patients. J Cancer 2020; 11(23):6850-6860. doi:10.7150/jca.48218. Available from http://www.jcancer.org/v11p6850.htm

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Abstract

Chemotherapy resistance remains a blockade for successful treatment and longer overall survival of patients with epithelial ovarian cancer (EOC). CTNNBIP1 is an inhibitor of β-catenin that is a chemotherapeutic target for EOC treatment. In the present study, we investigated associations between single nucleotide polymorphisms (SNPs) of CTNNBIP1 and platinum treatment response of Han Chinese EOC patients and subsequently performed functional prediction and validation of the resultant SNPs. We found that CTNNBIP1 rs935072 AT/TT variant genotypes were associated with platinum treatment response in the multivariate logistic regression analysis of EOC patients. Specifically, the CTNNBIP1 rs935072 AT/TT genotypes were associated with a decreased risk of developing chemoresistance ([adjusted odds ratio (OR)] = 0.89, 95% confidence interval (CI) = 0.82-0.97 and P=0.010), compared with the AA genotype. Further experiments showed that the underlying mechanism for the CTNNBIP1 rs935072 A>T change in chemotherapy treatment response resulted from a lower binding affinity of miR-27a-3p, thereby leading to up-regulation of the CTNNBIP1 expression. We further found that overexpression of CTNNBIP1 sensitized ovarian cancer cells to platinum treatment. Thus, the present study provides evidence that functional variants of CTNNBIP1 may regulate the expression of CTNNBIP1, a possible mechanism affecting platinum treatment response of EOC patients.

Keywords: genetic variants, single nucleotide polymorphisms, ovarian cancer, CTNNBIP1, platinum treatment response