Methylation profile of colon cancer genes in colorectal precursor lesions and tumor tissue: perspectives for screening.

AIMS

Epigenetic alterations of genes involved in colorectal carcinogenesis are likely to be informative biomarkers for early detection. We assessed the methylation profile of a panel of seven colon cancer-related genes comparing normal colon, colorectal cancer (CRC) precursor lesions and cancer tissues from a Brazilian cohort.

METHODS

The cohort comprised 114 CRC patients, including 40 matched normal tissue, 47 patients with adenomas, 33 with serrated polyps and 8 with normal colonic biopsy. DNA methylation status of , , , , , and was determined by pyrosequencing and correlated with clinicopathological features. Sensitivity, specificity, positive predictive value and negative predictive value were calculated for all genes using cancer endpoint.

RESULTS

The most frequently methylated genes in cancer and in precancer lesions were , , and , ranging from 55.3 to 95% of the samples. Overall, the frequency of methylation of these four genes in normal colonic tissue was significantly lower as compared to cancer or precursor lesions both in adenoma-carcinoma ( < .001 and  < .050) and serrated (sessile-serrated lesion) ( < .001 and  < .050) pathways. Additionally, sensitivity for the cancer endpoint ranged from 65.6 to 91.8%, and specificity from 17.9 to 62.9% for , , , and genes. Moreover, the comethylation of ≥4 genes was higher in sessile-serrated lesion (87.5%) and conventional adenomas (78.7%) than in hyperplastic polyps (43.7%) ( = .025) and was significantly associated with proximal cancers ( = .042).

CONCLUSIONS

Our study suggests the DNA methylation can constitute potential biomarkers in CRC screening of Brazilian population.