The major limitation of the present work was its retrospective nature. Moreover, it is noteworthy that most HCC patients in China have a hepatitis B virus-positive background, which differs from studies in Japan, Europe, and the United States. To the best of our knowledge, this is the first paper demonstrating the implications of 5-hmC and IDH2 in HCC. Our findings indicate that a high expression of 5-hmC and IDH2 predicts comparably less aggressive tumor behavior. Importantly, 5-hmC expression (particularly when combined with IDH2 expression) enables us to more accurately predict the true prognosis of HCC patients. Moreover,

given the proposed epigenetic nature of 5-hmC and IDH2, the therapeutic manipulation of 5-hmC and IDH2 will assist in guiding clinical strategies. Conclusions In summary, 5-hmC and IDH2 correlate with PKA activator less aggressive tumor behavior in HCC. Low 5-hmC or IDH2 expression alone and combined 5-hmC and IDH2 expression were associated with lower OS rates and higher cumulative recurrence rates. When 5-hmC and IDH2 are considered together, they serve as a prognostic marker in patients with surgically resected HCCs. Acknowledgments Financial support by the grants from National Natural Science Foundation of China (No.81272389, 81030038); National Key Sci-Tech Project (2012ZX10002011-002); And Scholarship Award

for Excellent Doctoral Student granted by Ministry of Education (JFF152005). Electronic supplementary material Additional file 1: Figure Bacterial neuraminidase S1: Diagram figure to summarize the biological NVP-BGJ398 chemical structure functions of IDH2 and 5-hmC. (DOC 55 KB) Additional file 2: Table S1: Summary of the clinicopathological features of the training and validation cohort. Table S2. Summary of the correlations of 5-hmC and IDH2 protein expression with clinicopathological features in validation cohort (N=328). Table S3. Summary of univariate and multivariate analyses of 5-hmC and IDH2 protein expression associated with survival and recurrence

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