单酰甘油脂肪酶高表达是肝细胞癌患者生存预后的独立指标

Monoacylglycerol lipase high expression as an independent indicator of survival for patients with hepatocellular carcinoma

目的研究单酰甘油脂肪酶(MAGL)在肝细胞癌患者组织中的表达水平及其临床相关性。方法对353例肝细胞肝癌(HCC)患者的肝癌和癌旁组织微芯片(TMA)进行针对MAGL蛋白的免疫组织化学检测,通过Image-Pro Plus 6.0对TMA中MAGL表达水平进行定量分析。比较肝癌组织及癌旁组织中MAGL表达差异。结合TMA纳入患者的临床随访资料,采用logistic回归分析TMA中MAGL蛋白表达水平与纳入患者HCC肿瘤分化程度及1年、3年生存率的相关性;Kaplan Meier法绘制并分析不同MAGL蛋白表达水平的患者生存曲线;多元线性回归分析MAGL蛋白表达水平与纳入患者生存时间的相关性;COX回归分析MAGL蛋白表达水平与纳入患者HCC死亡风险的相关性。结果MAGL在HCC组织中的表达明显高于癌旁组织。MAGL蛋白表达水平与患者HCC肿瘤分化程度(P < 0.001)及1年生存率(P = 0.01)存在相关性,而与3年生存率未见明显相关性(P = 0.91);生存曲线显示MAGL表达水平与HCC患者预后生存呈负相关(P = 0.001);多元线性回归显示MAGL表达水平与HCC患者的总体生存时间呈负相关(P = 0.010,R2 = 0.166,Durbin-Watson值:1.989);COX回归显示MAGL表达水平是HCC患者死亡的风险因子[P = 0.004,Exp(B)= 1.000]。结论MAGL表达水平与HCC患者肿瘤恶性程度呈正相关,且与其预后呈负相关,因此MAGL可作为HCC患者预后的新的预测指标。

Objective To study the expression level of monoacylglycerol lipase (MAGL) in liver tissues of patients with hepatocellular carcinoma (HCC), and its clinical correlation. Methods Immunohistochemistry was employed to detect MAGL protein in 353 cases with hepatocellular carcinoma (HCC) and tissue microarray (TMA) for paracancerous liver tissues. The expression levels of MAGL in TMA were quantitatively analyzed using Image-Pro plus 6.0. The difference in MAGL expression between liver cancer tissues and paracancerous liver tissues was compared. Combined with the clinical follow-up data of TMA patients, the correlation between the expression of MAGL in TMA and the degree of HCC tumors differentiation and the survival rate of 1-year and 3-year were analyzed using Logistic regression analysis. The survival curves of patients with different levels of MAGL protein was plotted and analyzed using Kaplan-Meier method. The expression of MAGL protein was analyzed by multiple linear regression analysis. COX regression was used to analyze the correlation between MAGL protein expression level and the risk of HCC death in the included patients. Results The expression of MAGL in HCC tissues was significantly higher than paracancerous liver tissues. The expression level of MAGL was correlated to the degrees of HCC tumors differentiation (P < 0.001) and 1-year survival rate (P = 0.01), but not with 3-year survival rate (P = 0.91). Survival curve showed that the expression level of MAGL was negatively correlated with prognosis and survival of HCC patients (P = 0.001). Multiple linear regressions showed a negative correlation between MAGL expression level and overall survival time of HCC patients (P=0.010, R2=0.166, Durbin-Watson value: 1.989). COX regression showed that the expression of MAGL was a risk factor for death of patients with HCC [P = 0.004, Exp (B)= 1.000]. Conclusion The expression level of MAGL has positive correlation with the malignant degree in HCC patients, and negative correlation with its prognosis. Therefore, MAGL may serve as a new prognostic indicator for HCC patients.