Chen Xi-Hua, Wu Wen-Guang, Ding Jian
Department of General Surgery, Cixi People's Hospital, No. 999, Nanerhuan Eastern Road, Hushan District, Cixi, 315300, China.
Tumour Biol. 2014 Feb;35(2):967-71. doi: 10.1007/s13277-013-1129-9. Epub 2013 Sep 5.
Recently, it has been reported that tazarotene-induced gene 1 (TIG1) methylation was frequently detected in a variety of human cancers. However, the relationship between the TIG1 methylation and the characteristics of hepatocellular carcinoma (HCC) remains unknown. The aim of present study was to observe the promoter methylation of TIG1 in HCC tissues and assess its prognostic significance for HCC. Real-time quantitative polymerase chain reaction and methylation-specific polymerase chain reaction were used, respectively, to examine the mRNA expression and methylation status of TIG1 in 91 pairs of HCC and adjacent noncancerous tissues. The mRNA expression level of TIG1 was significantly lower in HCC tissues than in adjacent noncancerous tissues. The rate of TIG1 promoter methylation was significantly higher in HCC tissues than in adjacent noncancerous tissues (P < 0.001). A strong correlation between downregulation and promoter methylation was found in these tumors (P < 0.001). More importantly, TIG1 methylation status was related to tumor size (P = 0.015), histological differentiation (P = 0.004), and tumor stage (P < 0.001). Kaplan-Meier survival analysis showed that TIG1 promoter hypermethylation was associated with a worse outcome in patients with HCC. Further, Cox multivariate analysis indicated that TIG1 methylation status was an independent prognostic factor for the overall survival rate of HCC patients. In conclusion, our data suggested that epigenetic silencing of TIG1 gene expression by promoter hypermethylation may play an important role in HCC.
最近，有报道称在多种人类癌症中经常检测到他扎罗汀诱导基因1（TIG1）甲基化。然而，TIG1甲基化与肝细胞癌（HCC）特征之间的关系仍不清楚。本研究的目的是观察HCC组织中TIG1的启动子甲基化情况，并评估其对HCC的预后意义。分别采用实时定量聚合酶链反应和甲基化特异性聚合酶链反应检测91对HCC组织及癌旁非癌组织中TIG1的mRNA表达及甲基化状态。HCC组织中TIG1的mRNA表达水平显著低于癌旁非癌组织。HCC组织中TIG1启动子甲基化率显著高于癌旁非癌组织（P < 0.001）。在这些肿瘤中发现下调与启动子甲基化之间存在强相关性（P < 0.001）。更重要的是，TIG1甲基化状态与肿瘤大小（P = 0.015）、组织学分化（P = 0.004）和肿瘤分期（P < 0.001）有关。Kaplan-Meier生存分析表明，TIG1启动子高甲基化与HCC患者预后较差相关。此外，Cox多因素分析表明，TIG1甲基化状态是HCC患者总生存率的独立预后因素。总之，我们的数据表明，启动子高甲基化导致的TIG1基因表达表观遗传沉默可能在HCC中起重要作用。
