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Carcinogenesis. 2019 May 13. pii: bgz092. doi: 10.1093/carcin/bgz092. [Epub ahead of print]

Functional genetic variants of RUVBL1 predict overall survival of Chinese patients with epithelial ovarian cancer.

Li H1,2, Tong X1,2, Xu Y1,2, Wang M1,2, Dai H3,4, Shi T5, Sun M6, Chen K3,4, Cheng X1,2,7, Wei Q1,8,9.

Author information

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 Pathology, Tissue Bank, Fudan University Shanghai Cancer Center, Shanghai, China.
7
Department of Gynecologic Oncology, 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.

Abstract

To date, the five-year overall survival of epithelial ovarian cancer (EOC) remains poor. Because studies suggest that RUVBL1 may be a chemotherapeutic target for treatment of cancer, in the present study, therefore, we investigated the role of potentially functional single nucleotide polymorphisms (SNPs) of RUVBL1 in survival of Chinese patients with EOC, and we subsequently performed functional prediction and validation of the identified significant SNPs. We found that RUVBL1 rs1057156 A>G and RUVBL1 rs149652370 A>G were associated with survival of EOC in the multivariate Cox proportional hazards regression analysis. Specifically, the RUVBL1 rs149652370 AG genotype was associated with a shorter progression free survival (PFS) ([adjusted hazards ratio (HR)]=3.32, 95% confidence interval (CI)=1.76-6.25 and P=2.01E-04), compared with the AA genotype. The RUVBL1 rs1057156 AG (only nine had GG) genotype were also associated with a poor overall survival (adjusted HR=1.73, 95% CI=1.19-2.52, P=0.004), compared with the AA genotype. Further experiments showed that the RUVBL1 rs1057156 A>G change lowered its binding affinity to microRNA-4294 and led to up-regulation of the RUVBL1 expression. We further found that overexpression of RUVBL1 promoted cell proliferation and metastatic potential. Overall, RUVBL1 enhanced EOC cell proliferation, invasion and migration presumably by stimulating the process of glycolysis. Thus, the present study provides evidence that functional variants of RUVBL1 may regulate its gene expression, a possible mechanism affecting survival of EOC patients and that RUVBL1 may be a potential chemotherapeutic target for treatment of EOC patients.

KEYWORDS:

RUVBL1 ; genetic variant; ovarian cancer; single nucleotide polymorphisms; survival

PMID:
31083717
DOI:
10.1093/carcin/bgz092

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