The Value and Clinical Significance of ZNF582 Gene Methylation in the Diagnosis of Cervical Cancer

Chunhe Zhang; Shaowei Fu; Luyue Wang; Fang Wang; Dan Wu; Xiangyi Zhe; Huizhen Xin; Hongtao Li; Dongmei Li; Fuyuan Jin; Renfu Shao; Zemin Pan

doi:10.2147/OTT.S277445

The Value and Clinical Significance of ZNF582 Gene Methylation in the Diagnosis of Cervical Cancer

Onco Targets Ther. 2021 Jan 14:14:403-411. doi: 10.2147/OTT.S277445. eCollection 2021.

Authors

Chunhe Zhang^#¹, Shaowei Fu^#¹, Luyue Wang^#¹, Fang Wang¹, Dan Wu¹, Xiangyi Zhe¹, Huizhen Xin¹, Hongtao Li¹, Dongmei Li¹, Fuyuan Jin¹, Renfu Shao², Zemin Pan¹

Affiliations

¹ Department of Biochemistry and Molecular Biology, School of Medicine, Shihezi University, Xinjiang Endemic and Ethnic Disease and Education Ministry Key Laboratory, Shihezi, Xinjiang 832002, People's Republic of China.
² School of Science, Technology and Engineering, Genecology Research Centre, University of the Sunshine Coast, Sippy Downs, Queensland 4556, Australia.

^# Contributed equally.

Abstract

Introduction: The aim of this study was to determine whether ZNF582 gene methylation and tissue protein expression can be used as a tool with high sensitivity and specificity for cervical cancer screening. We analyzed the correlation between promoter methylation of ZNF582 gene and cervical cancer and high risk HPV16/18 infection.

Methods: Tissue samples of normal cervical or chronic cervicitis (n=51), CIN (cervical intraepithelial neoplasia) (n=35), and cervical carcinoma (n=68) were tested for HPV16/18 infection by polymerase chain reaction (PCR). We also detected the methylation status of the ZNF582 gene promoter in the same tissues by methylation-specific PCR (MSP), then analyzed the correlation between ZNF582 promoter methylation and HPV16/18 infection. Immunohistochemistry was used to analyze ZNF582 gene expression in 152 cervical tissues. We detected ZNF582 mRNA expression in cervical tissues (including cancer and non-cancer) by real-time fluorescence quantitative PCR (qPCR).

Results: Among 93 high-grade cervical lesions (CINII and above) and cervical cancer samples, 57 cases were positive for HPV16/18 infection and 36 cases were negative. ZNF582 gene methylation occurred in 9 out of 51 cases in normal cervical tissues (17.6%), 16 of 35 cases in CIN tissues (45.7%), and 50 of 68 cases in cervical cancer (73.5%). The differences in methylation rate of the three groups were statistically significant (P<0.05). The ZNF582 methylation rate in the positive HPV16/18 infection group was 73.7%, while the negative group was 63.9%. Compared with normal tissues, ZNF582 protein was highly expressed in cervical cancer tissues, but mRNA expression was low.

Conclusion: While ZNF582 protein is highly expressed in cervical cancer tissues, it was not sufficient for use as a standard for cervical cancer staging. On the other hand, ZNF582 promoter methylation had high specificity and sensitivity in detecting CINII and highly diseased cervical lesions and could be used as a diagnostic marker for cervical cancer of women.

Keywords: HPV16/18; ZNF582 gene; cervical cancer; gene expression; promoter methylation.

Grants and funding

We acknowledge funding support from the International Science and Technology Collaboration Projector of Xinjiang Production and Construction Corps (grant numbers 2019BC007), the National Natural Science Foundation of China (grant numbers: U1503125, 81660462), the Youth Project Development and Regeneration Key Laboratory of Sichuan Province, the General Project Scientific Research Fund of Chengdu Medical College (grant number: SYS18-07), and the Xinjiang Production and Construction Corps Key Areas Innovation Team Project (grant number: 2018CB002).