Uncovering potential genes in colorectal cancer based on integrated and DNA methylation analysis in the gene expression omnibus database

Abstract

Background Colorectal cancer (CRC) is major cancer-related death. The aim of this study was to identify differentially expressed and differentially methylated genes, contributing to explore the molecular mechanism of CRC. Methods Firstly, the data of gene transcriptome and genome-wide DNA methylation expression were downloaded from the Gene Expression Omnibus database. Secondly, functional analysis of differentially expressed and differentially methylated genes was performed, followed by protein-protein interaction (PPI) analysis. Thirdly, the Cancer Genome Atlas (TCGA) dataset and in vitro experiment was used to validate the expression of selected differentially expressed and differentially methylated genes. Finally, diagnosis and prognosis analysis of selected differentially expressed and differentially methylated genes was performed. Results Up to 1958 differentially expressed (1025 up-regulated and 993 down-regulated) genes and 858 differentially methylated (800 hypermethylated and 58 hypomethylated) genes were identified. Interestingly, some genes, such as GFRA2 and MDFI, were differentially expressed-methylated genes. Purine metabolism (involved IMPDH1), cell adhesion molecules and PI3K-Akt signaling pathway were significantly enriched signaling pathways. GFRA2, FOXQ1, CDH3, CLDN1, SCGN, BEST4, CXCL12, CA7, SHMT2, TRIP13, MDFI and IMPDH1 had a diagnostic value for CRC. In addition, BEST4, SHMT2 and TRIP13 were significantly associated with patients’ survival. Conclusions The identified altered genes may be involved in tumorigenesis of CRC. In addition, BEST4, SHMT2 and TRIP13 may be considered as diagnosis and prognostic biomarkers for CRC patients.

Co-Occurrence of Beckwith–Wiedemann Syndrome and Early-Onset Colorectal Cancer

“…The methylome analysis revealed a general epigenome instability of the neoplastic tissue, showing primary or CNV-dependent methylation changes across the whole genome and involving tumor-associated genes and imprinted loci ( Figure 3 and Table S4 ). Notably, several DMGs belonged to the WNT signaling, Cell adhesion, Neuroactive ligand-receptor interaction and Calcium signaling pathways, in accordance with previously reported CRC methylome data [ 31 , 32 ]. These pathways have all been reported to play a crucial role in the onset of CRC or in driving its progression [ 18 , 32 , 33 ].…”

Tissue-specific atlas of trans-models for gene regulation elucidates complex regulation patterns

“…There are several TFs in their models across these digestive system tissues, but the most highly weighted TFs are RNA Polymerase I Subunit A (POLR1E) and genes from the Signal Transducer And Activator Of Transcription family STAT2, STAT3 and STAT4. Indeed, POLR1E is part of enriched signaling pathways in colorectal cancer [ 26 , 27 ] while these member of the STAT family are contributing to promotion of colorectal tumorigenesis, silencing them inhibits cell proliferation and invasion of colorectal cancer cells, and considered as targets for therapy [ 27 – 34 ].…”

The Expression of the Claudin Family of Proteins in Colorectal Cancer

“…Although there are conflicting reports regarding CLDN1 expression in CRC, the majority of data suggests that CLDN1 is upregulated in CRC. At the RNA level, seventeen independent groups reported the upregulation of CLDN1 in CRC compared to the normal colon [ 34 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 ]. This upregulation was found to occur at all stages of CRC, including metastases [ 41 , 42 ].…”