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

Abstract

Ovarian cancer is the leading cause of death from gynecologic cancers, but platinum resistance remains a major obstacle in the chemotherapy of ovarian cancer. This study aims to examine the role of polymorphisms in sulfatase 1 (SULF1) in platinum resistance and survival in advanced epithelial ovarian cancer (EOC) patients. We genotyped 12 SNPs of SULF1 in 195 EOC patients treated with platinum using MassARRAY method and evaluated the association between the SNPs and platinum response. SULF1 rs3802278 was marginal significantly associated with platinum resistance in recessive model with p value of 0.055. The patients with SULF1 rs3802278 AA were more resistant to platinum-based chemotherapy comparing to those with AG/GG genotype (OR: 2.317, 95%CI: 0.982 ∼ 5.465). In survival analysis, rs3802278 was significantly associated with both of PFS and OS after adjusted by FIGO stage and age. Patients with AA genotypes showed a shorter PFS and OS than with AG/GG genotypes (median PFS: 15 months vs. 21 months, p = 0.010, HR = 1.876, 95%CI: 1.165-3.022; median OS: 42 months vs. 73 months, p = 0.031, HR = 1.928, 95%CI: 1.061-3.504). SULF1 rs3802278 may serve as a potential candidate biomarker for the prediction of platinum resistance and prognosis in Chinese EOC patients.

Keywords:

• SULF1
• polymorphism
• chemotherapy
• platinum resistance
• survival
• epithelial ovarian cancer

Disclosure statement

The authors declare that there are no conflicts of interest.

Author contributions

Participated in research design: Yingzi Liu. Statistical analysis: Qianying Ouyang, Yujie Liu, Xi Li. Conducted experiments: Zeen Sun, Qianying Ouyang, Yujie Liu. Performed clinical data analysis: Feiyue Zeng; Keqiang Zhang. Wrote or contributed to the writing of the manuscript: Feiyue Zeng, Xi Li, Yingzi Liu.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (81974512), the Hunan Natural Science Foundation (2019JJ40485, 2020JJ4894).

Notes on contributors

Feiyue Zeng

Feiyue Zeng, Ph.D. Doctor-in-charge of Department of Radiology, Xiangya Hospital, Central South University. Main research areas: Tumor resistance.

Yujie Liu

Yujie Liu, PhD candidate of Department of Clinical Pharmacology, Xiangya Hospital, Central South University. Main research areas: Phamacogenomics.

Qianying Ouyang

Qianying Ouyang, PhD candidate of Department of Clinical Pharmacology, Xiangya Hospital, Central South University. Main research areas: Phamacogenomics.

Zeen Sun

Zeen Sun, Master candidate of Department of Clinical Pharmacology, Xiangya Hospital, Central South University. Main research areas: Phamacogenomics.

Keqiang Zhang

Keqiang Zhang, Ph.D, Director physician of Department of Gynaecology, TheAffiliated Tumor Hospital of Xiangya Medical School, Central South University. Main research areas: Gynecologic oncology.

Xi Li

Xi Li Ph.D. Associate professor of Department of Clinical Pharmacology, Xiangya Hospital, Central South University. Main research areas: Phamacogenomics, Pharmacomicrobiomics and Bioinformatics.

Yingzi Liu

Yingzi Liu, Ph.D. Associate professor of Department of Clinical Pharmacology, Xiangya Hospital, Central South University. Main research areas: Phamacogenomics.