DNA hydroxymethylation of colorectal primary carcinoma and its association with survival

Methods

A total of 71 cases of colorectal carcinoma with hepatic metastasis were enrolled from the Department of Pathology of SIR RUN RUN SHAW Hospital. Paired primary tumors, hepatic metastases, and normal mucosa samples were collected from formalin-fixed paraffin-embedded tissues by manual macrodissection. And global levels of DNA methylation and hydroxymethylation in these tissues, measured by an ELISA-like microplate-based colorimetric methods. The immunohistochemical expression of 5-methylcytosine and 5-hydroxymethylcytosine were analyzed also.

Results

The levels of DNA methylation in both primary and metastatic tumors were elevated when compared with normal mucosa, while DNA hydroxymethylation decreased slightly in those tissues. Similar results were observed in immunohistochemical staining. DNA methylation in hepatic metastases differed significantly in lymph node metastases (P = 0.037). And DNA hydroxymethylation in colorectal primary carcinoma was significantly different between tumor grade group (P = 0.018) and gender group (P = 0.048) respectively. And survival analyzes revealed that higher levels DNA hydroxymethylation were associated with better prognosis in colorectal primary carcinoma (P < 0.05).

Conclusion

DNA hydroxymethylation correlated with less aggressive tumor behavior in colorectal cancer and were identified as an independent prognostic factor in patients' overall survival, and downregulation of DNA hydroxymethylation may serve as a useful biomarker for colorectal cancer prognosis evaluation.

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