Identification of Prognostic Biomarkers for Bladder Cancer Based on DNA Methylation Profile

Shumei Zhang; Jingyu Zhang; Qichao Zhang; Yingjian Liang; Youwen Du; Guohua Wang

doi:10.3389/fcell.2021.817086

Identification of Prognostic Biomarkers for Bladder Cancer Based on DNA Methylation Profile

Front Cell Dev Biol. 2022 Jan 31:9:817086. doi: 10.3389/fcell.2021.817086. eCollection 2021.

Authors

Shumei Zhang¹, Jingyu Zhang², Qichao Zhang¹, Yingjian Liang^{3

4}, Youwen Du⁵, Guohua Wang¹

Affiliations

¹ College of Information and Computer Engineering, Northeast Forestry University, Harbin, China.
² Department of Neurology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
³ Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
⁴ Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
⁵ School of Life Sciences, Anhui Medical University, Hefei, China.

Abstract

Background: DNA methylation is an important epigenetic modification, which plays an important role in regulating gene expression at the transcriptional level. In tumor research, it has been found that the change of DNA methylation leads to the abnormality of gene structure and function, which can provide early warning for tumorigenesis. Our study aims to explore the relationship between the occurrence and development of tumor and the level of DNA methylation. Moreover, this study will provide a set of prognostic biomarkers, which can more accurately predict the survival and health of patients after treatment. Methods: Datasets of bladder cancer patients and control samples were collected from TCGA database, differential analysis was employed to obtain genes with differential DNA methylation levels between tumor samples and normal samples. Then the protein-protein interaction network was constructed, and the potential tumor markers were further obtained by extracting Hub genes from subnet. Cox proportional hazard regression model and survival analysis were used to construct the prognostic model and screen out the prognostic markers of bladder cancer, so as to provide reference for tumor prognosis monitoring and improvement of treatment plan. Results: In this study, we found that DNA methylation was indeed related with the occurrence of bladder cancer. Genes with differential DNA methylation could serve as potential biomarkers for bladder cancer. Through univariate and multivariate Cox proportional hazard regression analysis, we concluded that FASLG and PRKCZ can be used as prognostic biomarkers for bladder cancer. Patients can be classified into high or low risk group by using this two-gene prognostic model. By detecting the methylation status of these genes, we can evaluate the survival of patients. Conclusion: The analysis in our study indicates that the methylation status of tumor-related genes can be used as prognostic biomarkers of bladder cancer.

Keywords: DNA methylation; bladder cancer; prognostic markers; protein-protein interaction network; survival analysis.