To detect the protein expression of DNMT1 and DNMT3b, and to explore the association of DNMT1/3b with the clinicopathology and prognosis of hepatocellular carcinoma.

Eighty-nine cases of hepatocellular carcinoma were detected by immunohistochemistry (IHC) for analysis of the correlation between DNMT1/3b expression and clinicopathologic parameters and the tumor-free survival and overall survival. And high-throughput gene chip technology was used to screen out DNMT1 and DNMT3b target genes.

Both DNMT1 and DNMT3b expressions existed in 63 cases while 5 cases had neither DNMT1 nor DNMT3b. Nine cases had positive DNMT1 and 12 had positive DNMT3b. High level expression of DNMT1/3b was associated with serum AFP (χ²=12.903, P=0.005), HBV (χ²=9.535, P=0.023), satellite opacities (χ²=9.574, P=0.023), tumor recurrence and metastasis, and overall survival. No association was found with sex, size of tumor, liver cirrhosis and tumor differentiation. By Kaplan-Meier analysis, survival time was shorter in the patients with DNMT1 and/or 3b overexpression than in those with negative DNMT1 and 3b. More than 2 000 DNMT1 and DNMT3b target genes were screened out through high-throughput gene chip technology, and 112 of which were involved in tumor invasion and metastasis.

The overexpression of DNMT1 and DNMT3b are significantly related to the clinical and pathological characteristics such as serum AFP, HBV, satellite opacities, tumor recurrence and metastasis, and survival rate in hepatocellular carcinoma, and they can regulate a various tumor related genes in promoting the malignant phenotype including recurrence and metastasis of hepatocellular carcinoma.