Colorectal cancer is the third most common cancer and a major cause of cancer-related deaths. Early detection of colonic lesions can reduce the incidence and mortality of colorectal cancer. ...Colonoscopy is the screening test for colorectal cancer with the highest efficacy, but its acceptance in the general public is rather low. To identify suitable tumor-derived markers that could detect colorectal cancer in blood samples, we analyzed the methylation status of a panel of genes in sera of affected patients.
Using methylation-specific quantitative PCR, we analyzed the methylation of ten marker genes in sera of healthy individuals and patients with colorectal cancer.
Only HLTF, HPP1/TPEF, and NEUROG1 DNA methylation was detectable in at least 50% of patients with colorectal cancers. Whereas HLTF and HPP1/TPEF preferentially detected advanced and metastasized colorectal cancers, NEUROG1 methylation was detectable in UICC stages I-IV at a similar rate. Compared with other methylation markers, such as ALX4, SEPT9, and vimentin, NEUROG1 shows a higher sensitivity for colorectal cancer at UICC stages I and II. At a specificity of 91%, NEUROG1 reached a sensitivity of 61% (confidence interval, 50.4-70.6%) for the detection of colorectal cancers. Furthermore, detection of NEUROG1 methylation was independent of age and gender.
Methylation of the NEUROG1 gene is frequently found in sera of patients with colorectal cancers independent of tumor stage. The quantitative detection of NEUROG1 DNA methylation in serum is a suitable approach for the non-invasive screening for asymptomatic colorectal cancer.
BACKGROUNDCpG island hypermethylation is a common epigenetic event in colorectal cancer. The presence of simultaneous methylation of multiple genes is associated with poor prognosis in many types of ...tumours including colorectal cancer. We have shown earlier that the hypermethylation of the genes HLTF and HPP1/TPEF are independent prognostic serum markers in colorectal cancer identifying patients with increased risk of death. The purpose of this study was to analyse whether these factors also identify patients at risk of disease recurrence after curative surgery.
METHODSPretherapeutic sera of 106 patients curatively resected for colorectal cancer with known 5-year follow-ups were analysed for the presence of methylation of the genes HLTF and HPP1/TPEF.
RESULTSHLTF serum methylation was associated with an increased risk of disease recurrence by a factor of 2.7 (95% confidence interval1.2–6.0; P=0.014). Multivariate analysis showed methylated HLTF serum DNA to be independently associated with poor outcome and a relative risk of disease recurrence of 2.5 (95% confidence interval1.1–5.6; P=0.023).
CONCLUSIONHere, we show for the first time that a DNA methylation-based surrogate marker can serve as a predictor of disease recurrence in colorectal cancer.
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