期刊
SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY
卷 56, 期 8, 页码 920-928出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/00365521.2021.1922744
关键词
Colorectal cancer; adenoma; serrated polyps; DNA methylation; biomarker; Brazil
资金
- Barretos Cancer Hospital
- CNPq Productivity (Brazil) fellowship
- Public Ministry of Labor Campinas (Research, Prevention, and Education of Occupational Cancer) in Campinas, Brazil
- Barretos Cancer Hospital internal (IEP) grant
Epigenetic alterations of SEPT9, ALX4, NDRG4, and BMP3 genes are common in colorectal cancer and precursor lesions, with significantly higher methylation frequencies in tumors compared to normal colon tissues. These genes show potential as informative biomarkers for early detection and screening of CRC in the Brazilian population.
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 SEPT9, ALX4, NDRG4, BMP3, APC, p16 and MLH1 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 SEPT9, ALX4, NDRG4, and BMP3, 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 (p < .001 and p < .050) and serrated (sessile-serrated lesion) (p < .001 and p < .050) pathways. Additionally, sensitivity for the cancer endpoint ranged from 65.6 to 91.8%, and specificity from 17.9 to 62.9% for SEPT9, ALX4, NDRG4, and BMP3 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%) (p = .025) and was significantly associated with proximal cancers (p = .042). Conclusions Our study suggests the DNA methylation can constitute potential biomarkers in CRC screening of Brazilian population.
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