黑色素瘤相关抗原A6在肝细胞癌中的表达及与预后的关系

Expression of melanoma-associated antigen A6 in hepatocellular carcinoma and its relationship with prognosis

摘要:

目的 探讨黑色素瘤相关抗原A6（MAGEA6）在肝细胞癌（HCC）组织中的表达及与预后的关系。方法 选取2013年2月—2016年10月海南省人民院收治入院的120例HCC患者为研究对象。分析受试者的年龄、性别、饮酒史、甲胎蛋白（AFP）、肿瘤直径、分化程度、TNM分期、肝功能Child-Pugh分级、淋巴结转移等临床资料。采用实时荧光定量聚合酶链反应检测MAGEA6和AMPK mRNA的表达，免疫组织化学法检测MAGEA6蛋白的表达。根据肿瘤组织MAGEA6 mRNA相对表达量的中位值，将HCC患者分为MAGEA6低表达组和高表达组。比较两组患者的临床病理特征，绘制两组患者的Kaplan-Meier生存曲线，采用一般多因素Cox回归分析影响HCC患者预后的独立危险因素，Pearson法分析MAGEA6 mRNA与AMPK mRNA表达的相关性。结果 肿瘤组织MAGEA6 mRNA相对表达量、MAGEA6阳性率、MAGEA6蛋白免疫组织化学法评分高于癌旁组织（P <0.05）。MAGEA6低表达组与高表达组HCC患者的年龄、性别、饮酒史、分化程度、Child-Pugh分级比较，差异无统计学意义（P >0.05）。两组在AFP、肿瘤直径、TNM分期、淋巴结转移方面比较，差异有统计学意义（P <0.05）。MAGEA6高表达组生存率低于低表达组（P <0.05）。一般多因素Cox回归分析结果显示，AFP ［H^R=2.183（95% CI：1.117，4.267）］、TNM分期［H^R=2.203（95% CI：1.174，4.133）］、MAGEA6 mRNA ［H^R=6.328（95% CI：1.516，26.404）］是影响HCC患者预后的独立危险因素（P <0.05）。肿瘤组织AMPK mRNA相对表达量低于癌旁组织（P <0.05）。AMPK mRNA与MAGEA6 mRNA表达呈负相关（r =-0.680，P =0.000）。结论 MAGEA6基因在肝细胞癌中高表达，是HCC患者预后的危险因素，其可能通过AMPK信号通路在HCC中发挥促癌作用。

Abstract:

Objective To explore the expression of melanoma-associated antigen A6 (MAGEA6) in hepatocellular carcinoma (HCC) tissues and its relationship with HCC prognosis.Methods A total of 120 HCC patients treated in Hainan Provincial People's Hospital from February 2013 to October 2016 were enrolled. The clinical data including age, sex, history of alcohol consumption, alpha fetoprotein (AFP) level, diameter of tumor, degree of tumor differentiation, TNM stage, Child-Pugh grade, and lymph node metastasis were recorded. The mRNA expressions of MAGEA6 and AMPK were detected via qPCR, and the protein expression of MAGEA6 was measured by immunohistochemistry (IHC). According to the median of the mRNA expression of MAGEA6 in HCC tissues, HCC patients were divided into MAGEA6 low-expression group and MAGEA6 high-expression group. The clinicopathological characteristics of HCC patients were compared between the two groups. Kaplan-Meier curves were used to analyze the cumulative survival rates of patients in the two groups. The independent prognostic factors of HCC were determined by multivariable Cox regression models. The correlation between MAGEA6 mRNA and AMPK mRNA was analyzed by the Pearson method.Results The relative mRNA expression of MAGEA6, the positive rate of MAGEA6, and the IHC score of MAGEA6 in tumor tissues of HCC patients were higher than those in adjacent tissues (P < 0.05). There was no significant difference in age, sex, history of alcohol consumption, the degree of tumor differentiation, and Child-Pugh grade between the MAGEA6 low-expression group and MAGEA6 high-expression group (P > 0.05), while they differed in AFP level, diameter of tumor, TNM stage, and lymph node metastasis (P < 0.05). The survival rate of MAGEA6 high-expression group was lower than that of MAGEA6 low-expression group (P < 0.05). The multivariable Cox regression analysis revealed that AFP level [H^R = 2.183 (95% CI: 1.117, 4.267) ], TNM stage [H^R = 2.203 (95% CI: 1.174, 4.133) ], and mRNA expression of MAGEA6 [H^R = 6.328 (95% CI: 1.516, 26.404) ] were independent risk factors for the prognosis of HCC patients (P < 0.05). The relative mRNA expression of AMPK in tumor tissues was lower than that in the adjacent tissues (P < 0.05). The AMPK mRNA level was negatively correlated with MAGEA6 mRNA level (r = -0.680, P = 0.000).Conclusions MAGEA6 gene is highly expressed in HCC, and represents a risk factor for HCC prognosis, which may be associated with the AMPK signaling pathway.