miR-504在原发性肝细胞癌中的表达及其临床意义

Expression and Clinical Significance of miR-504 in Primary Hepatocellular Carcinoma

背景:microRNA表达失调与肿瘤的形成相关。miR-504在多种肿瘤中表达,但在肝癌中的表达目前尚未见相关报道。目的:探讨miR-504在原发性肝细胞癌(HCC)和肝癌细胞株中的表达及其与预后的关系。方法:收集85例HCC患者手术标本,常规培养5株肝癌细胞株和永生化肝细胞株。以CCK8法检测miR-504表达对HepG 2细胞增殖的影响,实时荧光定量PCR法检测miR-504表达,分析miR-504表达与HCC患者临床病理特征和预后的关系。结果:与正常肝细胞相比,5种肝癌细胞中miR-504表达显著降低(P<0.05)。上调miR-504表达明显抑制HepG 2细胞增殖,而下调miR-504表达则促进细胞增殖。HCC患者miR-504表达显著低于相应癌旁组织,且与肿瘤分化程度(P=0.002)、TNM分期(P=0.021)、甲胎蛋白(P=0.012)和门静脉癌栓(P=0.003)密切相关,但与患者的性别、年龄、肿瘤大小、肿瘤数量无关。miR-504低表达者的生存时间较高表达者明显缩短(P<0.05)。结论:miR-504在HCC中表达下调,其表达与患者的临床预后相关,提示miR-504可作为判断HCC患者预后的独立预测因子。

Background: Dysregulation of microRNA expression is involved in the carcinogenesis of many tumors,expression of miR-504 has been observed in many tumors,but its expression in primary hepatocellular carcinoma( HCC) has not been reported. Aims: To explore the expression and clinical significance of miR-504 in HCC tissues and cells. Methods:Tumor and para-cancerous tissue in 85 HCC patients were collected. Five liver cancer cell lines and immortalized liver cell line were conventionally cultured. Effect of miR-504 expression on HepG 2 cells proliferation was determined by CCK8 assay. The expression of miR-504 was determined by real time fluorescent quantitative PCR. Relationships between expression of miR-504 and clinicopathological features and prognosis of HCC patients were analyzed. Results: Compared with normal liver cells,expression of miR-504 was significantly downregulated in five liver cancer cells( P < 0. 05). Upregulation of miR-504 inhibited proliferation of HepG 2 cells,and down-regulation of miR-504 promoted proliferation of HepG 2 cells. miR-504 expression in tumor tissue was significantly decreased than that in corresponding para-cancerous tissue. Expression of miR-504 was correlated with tumor differentiation( P = 0. 002),TNM stage( P = 0. 021),alpha fetoprotein( P = 0. 012) and portal vein tumor thrombus( P = 0. 003),but not with gender,age,tumor size and tumor number. Survival in HCC patients with lower miR-504 expression was significantly shorter than that in patients with high expression( P < 0. 05). Conclusions: Expression of miR-504 is downregulated in HCC,and is correlated with the prognosis of patients,suggesting that miR-504 can be used as an independent predictor for prognosis of HCC patients.