IL-10 promoter hypomethylation is associated with increased IL-10 expression and poor survival in hepatocellular carcinoma

Background: Epigenetic alterations of tumor-associated genes contribute to the pathogenesis of virtually all cancer types. We evaluated the methylation status of the interleukin-10 (IL-10) gene promoter and assessed its association with IL-10 mRNA expression and clinical prognosis in hepatocellular carcinoma (HCC) patients. Methods: Methylation-specific polymerase chain reaction (MSP) and real-time polymerase chain reaction (PCR) were used to define the methylation index (MI) of the IL-10 gene and quantify IL-10 mRNA expression in 120 HCC samples and paired non-tumor tissues. Results: Mean MI was 0.47 in HCC specimens and 0.59 in non-tumor controls, and was associated with metastasis classification and serum alpha-fetoprotein (AFP) levels. IL-10 mRNA levels [mean-Delta Delta Ct of 1.678 in HCC cases with hypomethylation (Delta MI <= 0) and -0.18 in HCC cases with hypermethylation (Delta MI >0)] also correlated with metastasis classification and serum AFP. An association was detected between IL-10 mRNA and its gene's MI in HCC. Also, an association was found between IL-10 hypomethylation, but not IL-10 mRNA expression and reduced postoperative HCC survival. Conclusions: These results indicate that IL-10 promoter hypomethylation is associated with increased IL-10 mRNA levels and indicative of poor survival in HCC.