Hypermethylation of Cyclin D2 Predicts Poor Prognosis of Hepatitis B Virus-Associated Hepatocellular Carcinoma after Hepatectomy.
Hypermethylation of Cyclin D2 Predicts Poor Prognosis of Hepatitis B Virus-Associated Hepatocellular Carcinoma after Hepatectomy.
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DOI：
10.1620/tjem.254.233
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Yu Qian;He Wang;Ying Zhang;Jing-Wen Wang;Yu-Chen Fan;Shuai Gao;Kai Wang
中科院分区：
文献类型：
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作者：
Yu Qian;He Wang;Ying Zhang;Jing-Wen Wang;Yu-Chen Fan;Shuai Gao;Kai Wang
由于肝癌的进展和高复发率，肝癌患者的预后仍然很差。细胞周期蛋白D2（CCND 2）在调节细胞周期中起着至关重要的作用;事实上，CCND 2的异常甲基化参与了肝细胞癌的发展。因此，我们的目的是研究B型肝炎病毒（HBV）相关肝细胞癌患者CCND 2甲基化水平，并评估其在肝切除术后的预后意义。总共入组了257名受试者（166名接受手术切除的肝细胞癌患者、61名慢性乙型肝炎（CH B）（CH B）患者和30名健康对照）。使用MethyLight定量测量外周血单核细胞中的CCND 2甲基化。我们发现HBV相关性肝癌患者CCND 2甲基化水平显著高于CHB患者（P < 0.001）或健康对照（P < 0.001）。在肝癌组中，CCND 2甲基化水平在门静脉侵犯、肿瘤早期复发、TNM III/IV期和肿瘤大小≥ 5 cm的患者中较高（P < 0.05）。此外，较高水平的CCND 2甲基化与较差的总生存期和无病生存期相关（分别为P = 0.005和P < 0.001）。多变量分析表明CCND 2甲基化是肝细胞癌患者切除术后早期肿瘤复发（P = 0.021）、总生存期（P = 0.022）和无病生存期（P < 0.001）的独立预后因素。总之，CCND 2的高甲基化可能具有预测HBV相关肝细胞癌患者肝切除术后不良预后和早期肿瘤复发的高风险的临床实用性。
Prognosis of patients with hepatocellular carcinoma remains poor because of progression of hepatocellular carcinoma and high recurrence rates. Cyclin D2 (CCND2) plays a vital role in regulating the cell cycle; indeed, aberrant methylation of CCND2 is involved in the development of hepatocellular carcinoma. Therefore, we aimed to investigate levels of CCND2 methylation in patients with hepatitis B virus (HBV)-associated hepatocellular carcinoma and to evaluate its prognostic significance after hepatectomy. In total, 257 subjects were enrolled (166 hepatocellular carcinoma patients undergoing surgical resection, 61 chronic hepatitis B (CHB) patients, and 30 healthy controls). CCND2 methylation in peripheral blood mononuclear cells was measured quantitatively using MethyLight. We found that CCND2 methylation levels in patients with HBV-associated hepatocellular carcinoma were significantly higher than in CHB patients (P < 0.001) or healthy controls (P < 0.001). Within the hepatocellular carcinoma group, CCND2 methylation levels were higher in patients with portal vein invasion, early tumor recurrence, TNM III/IV stage, and tumor size ≥ 5 cm (P < 0.05). Furthermore, higher levels of CCND2 methylation were associated with worse overall survival and disease-free survival (P = 0.005 and P < 0.001, respectively). Multivariate analysis identified CCND2 methylation as an independent prognostic factor for early tumor recurrence (P = 0.021), overall survival (P = 0.022), and disease-free survival (P < 0.001) in hepatocellular carcinoma patients after resection. In conclusion, hypermethylation of CCND2 may have clinical utility for predicting a high risk of poor prognosis and early tumor recurrence in patients with HBV-associated hepatocellular carcinoma after hepatectomy.