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Epigenetic profiling and mRNA expression reveal candidate genes as biomarkers for colorectal cancer
- Source :
- Journal of Cellular Biochemistry. 120:10767-10776
- Publication Year :
- 2019
- Publisher :
- Wiley, 2019.
-
Abstract
- Colorectal cancer (CRC) is characterized by DNA methylation, which is associated with genomic instability and tumor initiation. As an important epigenetic regulation, DNA methylation can be used as a potential therapeutic target for CRC. In our study, we downloaded DNA methylation profiles (GSE17648 and GSE29490) and RNA sequencing microarray data (GSE25070 and GSE32323) from the Gene Expression Omnibus (GEO) database. As a result, 14 aberrantly methylated differentially expressed genes (DEGs) were screened according to the different criteria. We further validated these DEGs in The Cancer Genome Atlas (TCGA) database and obtained Pearson's correlation coefficient (COR) for the relationship between gene expression and DNA methylation. Three candidate genes (SOX9, TCN1, and TGFBI) with COR greater than 0.3 were screened out as Hub genes. The receiver operating characteristic result indicated that SOX9 and TGFBI effectively serve as biomarkers for the early diagnosis of CRC. Furthermore, the potential prognosis of the Hub genes for CRC patients was evaluated. Only TGFBI, which is regulated by methylation, can predict patient disease-free survival. Additionally, we examined the methylation level of the Hub genes in CRC cells in the Cancer Cell Line Encyclopedia database. Considering that methylation status tends to be highly modified on CpG islands in tumorigenesis, we screened the CpG island methylation of TGFBI based on the TCGA database and verified its diagnostic value in the GEO database. Our result revealed two Hub genes (TCN1 and TGFBI) whose aberrant expressions were regulated by DNA methylation. Additionally, we uncovered the hypermethylation of TGFBI on CpG islands and its clinical value in the diagnosis of CRC.
- Subjects :
- 0301 basic medicine
Candidate gene
Biology
medicine.disease_cause
Biochemistry
Epigenesis, Genetic
03 medical and health sciences
Atlases as Topic
0302 clinical medicine
Transforming Growth Factor beta
Cell Line, Tumor
Databases, Genetic
Biomarkers, Tumor
medicine
Humans
RNA, Messenger
Epigenetics
Molecular Biology
Early Detection of Cancer
Neoplasm Staging
Extracellular Matrix Proteins
Transcobalamins
Microarray analysis techniques
Gene Expression Profiling
SOX9 Transcription Factor
Cell Biology
Methylation
DNA Methylation
Survival Analysis
Gene Expression Regulation, Neoplastic
030104 developmental biology
CpG site
030220 oncology & carcinogenesis
DNA methylation
Cancer research
CpG Islands
Colorectal Neoplasms
Carcinogenesis
Signal Transduction
TGFBI
Subjects
Details
- ISSN :
- 10974644 and 07302312
- Volume :
- 120
- Database :
- OpenAIRE
- Journal :
- Journal of Cellular Biochemistry
- Accession number :
- edsair.doi.dedup.....32e2845a21189fb2c89c4b5f40fac154