| Summary: | 博士 === 國防醫學院 === 生命科學研究所 === 104 === Colorectal cancer (CRC), a common cause of death around the globe, is increasingly recognized as a critical public health issue. CRC is the first most commonly diagnosed cancer in males and the second in females, and age-standardized incidence rates are 59.62 (per 100,000) and 40.56 (per 100,000), respectively. The 5-year survival rate of CRC ranges from between 91% and 80% at histological stages I and II to approximately 61.7% and 23.2% at histological stages III and IV. However, the current guidelines for the assessment of the prognosis of CRC patients emphasize the classification of individual tumor-node-metastasis elements, which was suggested the need for further stratification of patients in the same tumor stage according to molecular factors. In order to have a potential clinical value in predicting cancer development and progression and in predicting the prognosis of cancer patients, the objectives of this study are to evaluate the DNA methylation status in patients with CRC and to investigate the association between prognosis and epigenetic factors as well as clinical stages among the patients. The hospital-based retrospective cohort study was performed to estimate the recurrence and mortality for 215 patients with CRC in Taiwan (mean age 64.32 years; 50.5% of men). The advanced stage patients with p16, hMLH1, and MGMT methylation were associated with higher risk of CRC recurrence compared with the local stage patients with unmethylation status in adjacent normal tissues, with adjusted hazard ratios (HRs) (95% confidence interval [CI]) of 10.85 (4.06–28.96), 9.04 (3.79–21.54), and 12.61 (4.90–32.44), respectively. For combined analyses, the risk of recurrence in the patients in advanced stage with DNA methylation in both normal and tumor tissues, compared with local stage with unmethylation, was increased with adjusted HR (95% CI) of 9.37 (3.36–26.09). In the advanced stage patients, methylation status and tissue subtype were associated with increased risk of 5-year cumulative CRC recurrence (p < 0.001). The ROC curve was further performed to analyze the determined prediction in relation to the risk of CRC recurrence (AUC = 0.877), with a sensitivity of 0.944% and a specificity of 0.649%. In conclusion, DNA methylation status would significantly increase the recurrence risk of CRC, with significant impact dependent on the interaction between DNA methylation and clinical stage, particularly in adjacent normal tissues. This study results also indicated an underlying mechanism for increased risk of recurrence in CRC patients, particularly in non-tumorous tissues.
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