Hepatocellular carcinoma (HCC) is the third most common cause of cancer death in the world. The US incidence of HCC has tripled between 1975 and 2005 and has been accompanied by improved long term survival rates, but as a result of HCC ‘s poor prognosis, 1-year survival remains lower than fifty percent. Therefore, a better understanding of the molecular mechanisms underlying the disease process is currently needed. Epigenetic alterations have been linked to HCC and global genomic hypomethylation is a well known hallmark of the disease. Less is understood about the role hydroxymethylation plays in HCC carcinogenesis. Here, we conducted a study to determine 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) levels by UPLC/MS/MS in HCC tumor (T) and non-tumor (NT) adjacent tissue DNAs of sixty six individuals treated at Columbia Presbyterian Medical Center in New York. We analyzed the association between demographic and clinicopathological characteristics and 5mC and 5hmC levels, as well as performed a Cox-survival analysis to determine which factors better predicted survival. Mean levels of 5mC (5mCT = 3.15±0.49% vs.5mCNT = 3.80±0.12% (p<0.0001) and 5hmC (5hmCT = 0.11±0.04% vs. 5hmCNT = 0.23±0.07%, p<0.0001) in tumor tissues were statistically significantly lower than in non-tumor tissues. Older age was associated with lower 5mC content (5mC<60y = 3.32±0.43% vs. 5mC≥60y = 3.00±0.50%, p = 0.001), while tumor DNA of transplant (LT) patients had higher 5hmC levels compared to surgical resection (LR) patients (5hmCLR = 0.10±0.04% vs. 5hmCLT = 30.13±0.04%, p = 0.0053). However, survival was predicted by whether transplant or resection were performed (Hazard ratio LT vs. LR, 3.54 (95% confidence interval:1.34-9.29), p = 0.01). Our study had a limited sample size, but suggests that future studies of 5hmC might be informative concerning HCC prognosis.

Citation Format: Lissette Delgado-Cruzata, Hui Chen Wu, Tiffany Thomas, Abby B. Siegel, Jing Shen, Yu-Jing Zhang, Abhishek Goyal, Christine C. Hsu, Helen Remotti, Regina M. Santella. Levels of 5-methyl-cytosine and 5-hydroxymethyl-cytosine in hepatocellular carcinoma prognosis. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4770. doi:10.1158/1538-7445.AM2015-4770

©2015 American Association for Cancer Research.
2015