Combined analysis and validation for DNA methylation and gene expression profiles associated with prostate cancer

Shixiong Deng,Yanqiu Tong,Yang Song

doi:10.1186/s12935-019-0753-x

Abstract

BackgroundProstate cancer (PCa) is a malignancy cause of cancer deaths and frequently diagnosed in male. This study aimed to identify tumor suppressor genes, hub genes and their pathways by combined bioinformatics analysis.MethodsA combined analysis method was used for two types of microarray datasets (DNA methylation and gene expression profiles) from the Gene Expression Omnibus (GEO). Differentially methylated genes (DMGs) were identified by the R package minfi and differentially expressed genes (DEGs) were screened out via the R package limma. A total of 4451 DMGs and 1509 DEGs, identified with nine overlaps between DMGs, DEGs and tumor suppressor genes, were screened for candidate tumor suppressor genes. All these nine candidate tumor suppressor genes were validated by TCGA (The Cancer Genome Atlas) database and Oncomine database. And then, the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses were performed by DAVID (Database for Annotation, Visualization and Integrated Discovery) database. Protein–protein interaction (PPI) network was constructed by STRING and visualized in Cytoscape. At last, Kaplan–Meier analysis was performed to validate these genes.ResultsThe candidate tumor suppressor genes were IKZF1, PPM1A, FBP1, SMCHD1, ALPL, CASP5, PYHIN1, DAPK1 and CASP8. By validation in TCGA database, PPM1A, DAPK1, FBP1, PYHIN1, ALPL and SMCHD1 were significant. The hub genes were FGFR1, FGF13 and CCND1. These hub genes were identified from the PPI network, and sub-networks revealed by these genes were involved in significant pathways.ConclusionIn summary, the study indicated that the combined analysis for identifying target genes with PCa by bioinformatics tools promote our understanding of the molecular mechanisms and underlying the development of PCa. And the hub genes might serve as molecular targets and diagnostic biomarkers for precise diagnosis and treatment of PCa.

Highlights

Prostate cancer (PCa) is a malignancy cause of cancer deaths and frequently diagnosed in male
By overlapping differentially expressed gene (DEG), differentially methylated gene (DMG) and TSGs, we identified some candidate tumor suppressor genes that can provide new ideas for diagnosis, therapy and biomarker studies in PCa
In order to better understand the molecular mechanism of candidate tumor suppressor genes and hub genes, gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) pathway and Protein–protein interaction (PPI) analysis were further performed

Summary

Introduction

Prostate cancer (PCa) is a malignancy cause of cancer deaths and frequently diagnosed in male. DNA methylation, one of the most important epigenetic factors, has been studied extensively over several decades, and its influence in a variety of human diseases, most malignancy tumor, diagnostic biomarkers and therapeutic targets, has been firmly measured and evaluated [1,2,3,4,5,6]. Tong et al Cancer Cell Int (2019) 19:50 gene expression by increasing transcription activity [8] This may be caused by blocking the intragenic promoter activity or affecting the methylation status of repetitive sequence within the transcription unit [9]. Prostate cancer (PCa) is the second most frequently diagnosed male-specific malignancy tumor in western countries. Illumina Infinium 450 k microarray and DNA microarray have utilized to investigate DNA methylation and gene expression in molecular mechanism, biological process, molecular diagnosis, tumor molecular, biomarker and drug targets discovery [13,14,15]

Objectives

Methods

Results

Discussion

Conclusion