DNA hypermethylated status and gene expression of / in patients with colorectal carcinoma.

BACKGROUND

Colorectal cancer (CRC) is a widespread and aggressive carcinoma with poor prognosis. Hypermethylation of specific gene promoters is an important mechanism of CRC. In this study, we investigated the hypermethylation of paired boxed gene 1 () and sex-determining region Y-related high-mobility group box 1 () genes in CRC tissues.

METHODS

DNA methylation at cg2,09,07,471 and cg0,66,75,478 from 166 cancer tissues and 37 normal tissues from CRC patients were compared using datasets downloaded from The Cancer Genome Atlas. Quantitative methylation-specific polymerase chain reaction and assay of and were performed in dissected tumor and paracancerous tissues by surgery from 41 CRC patients. Quantitative reverse transcription polymerase chain reaction and immunohistochemistry assay were performed in both CRC and paired normal tissues to detect mRNA and protein expression, respectively.

RESULTS

Methylation levels of / genes were significantly higher in cancer tissues than in paired normal tissues. and genes were methylated in 28 (68.3%) of the 41 CRC samples but in 5 (12.2%) and 0 (0%) of the paired normal control samples (both <0.001), respectively. Sensitivities and specificities of methylation for the detection of cancer were 68.3% and 87.8%, respectively, whereas the corresponding values for were 68.3% and 100%. However, the Kaplan-Meier analysis illustrated no significant difference in the overall survivals between patients with high and low methylation levels of or (>0.5). In addition, the methylation level of / was significantly higher in CRC patients with high TNM stage (TNM stage III/IV, 3.11±2.43) than those with low TNM stage (TNM stage I/II, 1.26±2.94, <0.05). Relative RNA and protein expression levels of / were both significantly lower in CRC tissues than in their paired normal tissue.

CONCLUSIONS

This study is the first analysis of the methylation of /, which may be new biomarkers for CRC screening.