Background Methylation plays an important role in colorectal cancer (CRC) pathogenesis. The goal of this study was to identify aberrantly differentially methylated genes (DMGs) and pathways through bioinformatics analysis among Iranian CRC patients using Methylation Next Generation Sequencing. Methods This study has integrated results of SureSelectXT Methyl-Seq Target with the potential key candidate genes and pathways in CRC. Six CRC and six samples of normal colon were integrated and deeply analyzed. In addition to this gene methylation profiling, several other gene methylation profiling datasets were obtained from Gene Expression Omnibus (GEO) and TCGA datasets. DMGs were sorted and candidate genes and enrichment pathways were analyzed. DMGs-associated protein–protein interaction network (PPI) was constructed based on the STRING online database. Results Totally, 320 genes were detected as common genes between our patients and selected GEO and TCGA datasets from the Agilent SureSelect analysis with selecting criteria of p-value < 0.05 and FC ≥ 1.5. DMGs were identified from hyper-DMGs PPI network complex and 10 KEGG pathways were identified. The most important modules were extracted from MCODE, as most of the corresponding genes were involved in cellular process and protein binding. Conclusions Hub genes including WNT2, SFRP2, ZNF726 and BMP2 were suggested as potentially diagnostic and therapeutic targets for CRC.

Background The incidence of colorectal cancer (CRC) has increased during recent years in Iran and other developing countries. Clinical studies suggest that essential folate dietary intake and moderate deficiency of methylenetetrahydrofolate reductase (MTHFR) may protect and reduce the risk of CRC. The present study aimed to investigate the clinical significance of C677T polymorphism within the MTHFR gene and its correlation with the serum folate and Vit B12 in the Iranian population suffering from CRC. Methods Blood samples were taken from 1017 Iranian individuals (517 cases and 500 controls) who were referred for colonoscopy. TaqMan probe assay was performed for C677T MTHFR polymorphism. Sera were fractionated from the blood samples of 43 patients and controls and folate and Vit B12 concentrations were measured by a monobind kit. The correlation of MTHFR polymorphisms and folate/vitamin-B12 with CRC risk was analyzed. Results In the current study, we found the frequency of three different genotypes of MTHFR polymorphism in the Iranian population i.e., CC, CT, and TT, to be 51.31, 26.73, 21.96 and 61, 32.2, 6.8 in case and control groups, respectively. The homozygote genotype of MTHFR rs1801133 polymorphism is associated with an increased risk of CRC by 3.68, 1.42, and 3.74-fold in codominant, dominant, and recessive models respectively (p value < 0.01). Our study revealed that there was no significant difference between the amount of folate and Vit B12 in the case and control groups (p value > 0.05). Conclusions This study revealed that there was no significant difference between the amount of folate and Vit B12 in the case and control groups. Furthermore, our results demonstrated a higher risk association for 677TT and 677TT + C677T genotypes of MTHFR compared with 677CC carriers among CRC patients.

Background: The incidence of colorectal cancer (CRC) has increased during recent years in Iran and other developing countries. Clinical studies suggest that essential folate dietary intake and moderate deficiency of methylenetetrahydrofolate reductase (MTHFR) may protect and reduce the risk of CRC.The aim of the present study was to investigate the clinical significance of C677T polymorphism within MTHFR gene and its correlation with the serum folate and Vit B12 in the Iranian population suffering from CRC.Methods: Blood samples were taken from 1017 Iranian individuals (517 cases and 500 controls) who were referred for colonoscopy. TaqMan probe assay was performed for C677T MTHFR polymorphism. Sera were fractionated from the blood samples of 43 patients and controls and folate and Vit B12 concentrations were measured by a monobind kit. The correlation of MTHFR polymorphisms and folate/vitamin-B12 with CRC risk were analyzed.Results: In the current study, we found the frequency of three different genotypes of MTHFR polymorphism in the Iranian population i.e., CC, CT and TT, to be 51.31, 26.73, 21.96 and 61, 32.2, 6.8 in case and control groups, respectively. The homozygote genotype of MTHFR rs1801133 polymorphism is associated with increased risk of CRC by 3.68, 1.42 and 3.74-fold in codominant, dominant and recessive models respectively (p value< 0.01). Our study revealed that there was no significant difference between the amount of folate and Vit B12 in case and control groups (p value> 0.05).Conclusions: This study revealed that there was no significant difference between the amount of folate and Vit B12 in the case and control groups. Furthermore, our results demonstrated a higher risk association for 677TT and 677TT+C677T genotypes of MTHFR compared with 677CC carriers among CRC patients.