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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.

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