Increased Trimethylation of histone H3K36 associates with biliary differentiation and predicts poor prognosis in resectable hepatocellular carcinoma.

Autor: Huang-Chun Lien, Yung-Ming Jeng, Yu-Ling Jhuang, Ray-Hwang Yuan
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: PLoS ONE, Vol 13, Iss 10, p e0206261 (2018)
Druh dokumentu: article
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0206261
Popis: INTRODUCTION:Trimethylation of histone H3K36 (H3K36me3), an epigenetic marker of transcription-associated histone modification and stem cell regulation, is expressed in a variety of human cancers. This study elucidated the prognostic significance of H3K36me3 in patients with resectable hepatocellular carcinoma (HCC). METHODS:Expression of H3K36me3 was retrospectively evaluated through immunohistochemistry in 152 surgically resected primary HCCs. RESULTS:In nontumorous liver parenchyma, H3K36Me3 was detected in bile ducts but not in hepatocytes. H3K36me3 was positive in 104 (68.4%) of the HCCs. Positivity for H3K36me3 was associated with high level of serum α-fetoprotein (>200 ng/mL, P = 0.0148), high tumor grade (P = 0.0017), and high tumor stage (P = 0.0008). Patients with H3K36me3-positive tumors were more likely to have lower 5-year disease-free survival and 5-year overall survival than those with H3K36me3-negative tumors (P = 0.0484 and P = 0.0213, respectively). Multivariate analysis showed that H3K36me3 positivity was an independent predictor of high tumor grade (P = 0.0475) and high tumor stage (P = 0.0114) and thus contributed to poor prognosis. Furthermore, H3K36me3 positivity was significantly correlated with the expression of biliary markers cytokeratin 19 (CK19) and hepatocyte nuclear factor 1β (HNF1β) (P < 0.0001 and P = 0.0005, respectively). Combinatorial analysis revealed that CK19 and HNF1β expression individually exerted additive prognostic adverse effects on HCCs with H3K36me3 positivity. CONCLUSIONS:Our study indicates that H3K36me3 positivity is associated with the expression of biliary markers and is a crucial predictor of poor prognosis in resectable HCC.
Databáze: Directory of Open Access Journals
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