Abstract
AimRectal adenocarcinoma (READ) is a malignancy cancer with the high morbidity and motility worldwide. Our study aimed to explore the potential pathogenesis of READ through integrated analysis of gene expression profiling and DNA methylation data.MethodsThe miRNA, mRNA expression profiling and corresponding DNA methylation data were downloaded from The Cancer Genome Atlas (TCGA) database. Differentially expressed mRNAs/ miRNAs/methylated regions (DEmRNA/DEmiRNAs) were identified in READ. The negatively correlation of DEmiRNA-DEmRNAs and DNA methylation-DEmRNAs were obtained. DEmRNAs expression was validated through quantitative real-time polymerase chain reaction (qRT-PCR) and microarray expression profiling analyses.Results1192 dysregulated DEmRNAs, 27 dysregulated DEmiRNAs and 6403 aberrant methylation CpG sites were screened in READ compared to normal controls. 1987 negative interaction pairs among 27 DEmiRNAs and 668 DEmRNAs were predicted. 446 genes with aberrant methylation were annotated. Eventually, 50 DEmRNAs (39 down- and 11 up-regulated DEmRNAs) with hypermethylation, synchronously negatively targeted by DEmiRNAs, were identified through the correlation analysis among 446 genes with aberrant methylation and 668 DEmRNAs. 50 DEmRNAs were significantly enriched in cAMP signaling pathway, circadian entrainment and glutamatergic synapse. The validation results of expression levels of DEmRNAs through qRT-PCR and microarray analyses were compatible with our study.Conclusion7 genes of SORCS1, PDZRN4, LONRF2, CNGA3, HAND2, RSPO2 and GNAO1 with hypermethylation and negatively regulation by DEmiRNAs might contribute to the tumorigenesis of READ. Our work might provide valuable foundation for the READ in mechanism elucidation, early diagnosis and therapeutic target identification.
Highlights
Colorectal cancer (CRC) is a leading cause of cancers with high morbidity and mortality
1192 dysregulated differentially expressed mRNAs (DEmRNAs), 27 dysregulated differentially expressed miRNAs (DEmiRNA) and 6403 aberrant methylation CpG sites were screened in Rectal adenocarcinoma (READ) compared to normal controls. 1987 negative interaction pairs among 27 DEmiRNAs and 668 DEmRNAs were predicted. 446 genes with aberrant methylation were annotated
50 DEmRNAs (39 down- and 11 up-regulated DEmRNAs) with hypermethylation, synchronously negatively targeted by DEmiRNAs, were identified through the correlation analysis among 446 genes with aberrant methylation and 668 DEmRNAs. 50 DEmRNAs were significantly enriched in cAMP signaling pathway, circadian entrainment and glutamatergic synapse
Summary
Colorectal cancer (CRC) is a leading cause of cancers with high morbidity and mortality. CRC is the third leading cause of cancer both in male and female and worldwide number of death in 2012 is more than 690,000 [1]. CRC is classified as colon cancer and rectum cancer according to the anatomical location. 20% of CRC patients lose opportunity for radical surgery on account of metastases [4]. Rectal cancer spreads more frequently to the thoracic organs, bone and nervous system and less frequently to peritoneum compared to colon cancer [5]. Gender, smoking and diabetes mellitus are risk factors of rectal cancer [6,7,8]
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have