Sun Feng-Kai, Sun Qi, Fan Yu-Chen, Gao Shuai, Zhao Jing, Li Feng, Jia Yi-Bin, Liu Chuan, Wang Li-Yuan, Li Xin-You, Ji Xiang-Fen, Wang Kai
Department of Hepatology, Qilu Hospital of Shandong University, Jinan, China.
Department of Hepatobiliary Surgery, Qilu Hospital of Shandong University, Jinan, China.
J Gastroenterol Hepatol. 2016 Feb;31(2):484-92. doi: 10.1111/jgh.13154.
Methylation of tissue factor pathway inhibitor 2 (TFPI2) gene has been detected in hepatocellular carcinoma (HCC). However, the clinicopathologcial significance and prognostic value of TFPI2 methylation in HCC remains largely unknown. This study aimed to investigate the prognostic value of TFPI2 methylation in HCC after hepatectomy.
Methylation status of TFPI2 gene was examined in 178 surgical specimens of HCC and 20 normal liver samples using methylation-specific polymerase chain reaction.
Methylation of TFPI2 gene was detected in 44.9% (80 of 178) of primary HCC samples, 10.7% (19 of 178) of the corresponding non-tumorous liver samples, and 5.0% (1/20) of the normal liver samples. The mRNA concentrations of TFPI2 in primary HCC tissues were significantly lower than those in corresponding non-tumorous liver tissues and those in normal liver tissues. TFPI2 methylation was significantly associated with higher TNM stage. Patients with TFPI2 methylation demonstrated a significantly poorer prognosis than those without TFPI2 methylation for both overall survival and disease-free survival (P < 0.001, respectively). Multivariate analyses confirmed that TFPI2 methylation was an independent prognostic factor for both overall survival (P = 0.002) and disease-free survival (P = 0.000) in HCC after hepatectomy. Moreover, TFPI2 methylation was found to be the only independent predictor for early tumor recurrence of HCC after resection based on multivariate analysis (P = 0.002).
Methylation of TFPI2 predicts high risk of advanced tumor stage, early tumor recurrence, and poor prognosis, and it could be a potential prognostic biomarker in patients with HCC after hepatectomy.
在肝细胞癌（HCC）中已检测到组织因子途径抑制物2（TFPI2）基因的甲基化。然而，TFPI2甲基化在HCC中的临床病理意义和预后价值仍大多未知。本研究旨在探讨肝切除术后TFPI2甲基化在HCC中的预后价值。
采用甲基化特异性聚合酶链反应检测178例HCC手术标本和20例正常肝组织样本中TFPI2基因的甲基化状态。
原发性HCC样本中44.9%（178例中的80例）检测到TFPI2基因甲基化，相应的非肿瘤肝组织样本中10.7%（178例中的19例）检测到，正常肝组织样本中5.0%（20例中的1例）检测到。原发性HCC组织中TFPI2的mRNA浓度显著低于相应的非肿瘤肝组织和正常肝组织中的浓度。TFPI2甲基化与较高的TNM分期显著相关。TFPI2甲基化的患者在总生存期和无病生存期方面的预后均明显差于未发生TFPI2甲基化的患者（P均<0.001）。多因素分析证实，TFPI2甲基化是肝切除术后HCC患者总生存期（P = 0.002）和无病生存期（P = 0.000）的独立预后因素。此外，基于多因素分析发现TFPI2甲基化是HCC切除术后早期肿瘤复发的唯一独立预测因素（P = 0.002）。
TFPI2甲基化预示着肿瘤晚期、早期肿瘤复发和预后不良的高风险，它可能是肝切除术后HCC患者潜在的预后生物标志物。
