Association of Histone Methyltransferase G9a and Overall Survival After Liver Resection of Patients With Hepatocellular Carcinoma With a Median Observation of 40 Months

Abstract

Approximately 50% of patients with hepatocellular carcinoma (HCC) reside in China. HCC is associated with very high mortality compared with other cancers. Although numerous factors influence the survival of patients with HCC who undergo liver resection, the role of the tumor biomarker histone methyltransferase (G9a) is unknown.We enrolled 350 patients with HCC who underwent liver resection and followed them for 40 months. Patients’ clinicopathologic characteristics were acquired from medical records, and overall survival was determined using multiple methods. We conducted an immunohistochemical analysis of study G9a expression in HCC tissues. We used χ2 test to evaluate the significance of the relationships between G9a and other factors and Cox proportional hazards regression to estimate the hazard ratios and 95% confidence intervals.The levels of alpha-fetoprotein were significantly higher in patients with G9a-positive tumors. TNM stage, elevated alpha-fetoprotein level, and G9a overexpression were associated with worse outcomes.High expression of G9a was associated with worse outcomes, indicating that G9a may serve as a prognostic biomarker for patients with HCC who undergo surgical resection. Because of its role in cell proliferation, G9a represents a potential therapeutic target.

H3K9 methyltransferases and demethylases control lung tumor-propagating cells and lung cancer progression

“…Since the discovery of potent G9a/Glp inhibitors, there has been an increase in studies investigating these enzymes in cancer. Indeed, much of the rationale for developing G9a/Glp inhibitors was that many tumors stained positively for these enzymes and this was often correlated with worse outcome 14 , 15 , 29 . It has been observed amongst almost all cancer models tested that G9a inhibition has antiproliferative effects, and different mechanisms have been proposed 9 , 10 .…”

Epigenetics in cancer stem cells

“…H3K9 methyltransferases, such as euchromatic histone lysine methyltransferase 2 (G9a/EHMT2) and euchromatic histone lysine methyltransferase 1 (GLP/EHMT1), catalyse mono- and di-methylation of the lysine residue, while tri-methylation of H3K9 is mediated by Suppressor of variegation 3–9 homolog 1 (SUV39H1) and Suppressor of variegation 3–9 homolog 2 (SUV39H2) [ 201 ]. Upregulation of G9a activity has been linked to several types of cancer, including ovarian, lung, liver and bladder cancers [ 202 – 208 ]. Hence, several substrate-competitive inhibitors of these HKMTs have been developed.…”

Clinicopathologic significance of protein lysine methyltransferases in cancer

“…EZH2 expression was an independent predictor of disease-specific survival after multivariate analysis (explanation of univariate/multivariate analysis in Explanation of staging and statistical terms section) including PR expression and positive lymph node status [5]. Similar findings Non-small cell lung cancer [25,26] No correlation data available Independent predictor of worse overall and recurrence-free survival in NSCLC Gastric cancer [27] Advanced clinical stage Lymph node metastasis Independent predictor of worse overall survival Hepatocellular carcinoma [28] No correlation data available Independent predictor of worse overall survival…”