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A Novel Prognostic DNA Methylation Panel for Colorectal Cancer

Colorectal cancer (CRC) is one of the most common cancers and the second leading cause of cancer-related deaths. Discrepancies in clinical outcomes are observed even among patients with same-stage CRC due to molecular heterogeneity. Thus, biomarkers for predicting prognosis in CRC patients are urgen...

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Published in:International journal of molecular sciences 2019-09, Vol.20 (19), p.4672
Main Authors: Chung, Hsin-Hua, Kuo, Chih-Chi, Hsiao, Cheng-Wen, Chen, Chao-Yang, Hu, Je-Ming, Hsu, Chih-Hsiung, Chou, Yu-Ching, Lin, Ya-Wen, Shih, Yu-Lueng
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Language:English
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Summary:Colorectal cancer (CRC) is one of the most common cancers and the second leading cause of cancer-related deaths. Discrepancies in clinical outcomes are observed even among patients with same-stage CRC due to molecular heterogeneity. Thus, biomarkers for predicting prognosis in CRC patients are urgently needed. We previously demonstrated that stage II CRC patients with methylation had poor 5-year overall survival. However, the methylation frequency of was only 23% in 151 pairs of CRC tissues. Thus, we aimed to develop a more robust prognostic panel for CRC using in combination with three genes: ( ), ( ), and ( ). Through quantitative methylation analysis, we found that , , and were hypermethylated in CRC tissues. methylation was significantly associated with poor 5-year overall, and disease-free survivals in stage I and II CRC patients. Sensitivity and specificity analyses of the four-gene combination revealed the best sensitivity and optimal specificity. Moreover, patients with the four-gene methylation profile exhibited poorer disease-free survival than those without methylation. A significant effect of the four-gene methylation status on overall survival and disease-free survival was observed in early stage I and II CRC patients ( = 0.0016 and = 0.0230, respectively). Taken together, these results demonstrate that the combination of the methylation statuses of , , , and creates a novel prognostic panel that could be considered a molecular marker for outcomes in CRC patients.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms20194672