原发性肝癌P-糖蛋白表达与肝动脉插管栓塞化疗疗效的关系及临床意义
Relationship between P-gp expression and clinical efficacy of transcatheter arterial embolization chemotherapy (TACE) in primary liver cancer and clinical significance

摘要：目的 检测肝癌细胞的多药耐药基因MDR1及编码产物P-gp(P-glycoprotein, P-gp)的表达并探讨其与原发性肝癌经肝动脉插管栓塞化疗(transcatheter arterial chemoembolization, TACE)疗效的关系及临床意义。方法 选取2010年6月到2013年6月来我院接受手术治疗的108例原发性肝癌患者作为肝癌组研究对象，同时选取来我院行肝穿刺检查的50例健康者作为对照。采用实时荧光定量PCR测定各组肝组织中MDR1的mRNA水平，并采用免疫组织化学法检测手术切除后的肝癌组织P-gp的表达。根据P-gp表达水平将患者分为耐药组和非耐药组，分析P-gp表达水平与原发性肝癌术后TACE治疗效果的关系。结果 与对照组比较，肝癌组患者肝脏组织中MDR1的mRNA表达水平显著升高(P<0.05)。其中肝癌组MDR1的mRNA/正常水平>2的患者76例，MDR1的mRNA/正常水平<2的患者32例。免疫组织化学结果显示P-gp呈棕黄色，主要表达于肝癌细胞的细胞膜表面。其中P-gp蛋白阴性患者(非耐药组)35例，阳性患者(耐药组)73例。非耐药组患者化疗有效率(74.28%)明显高于耐药组患者(43.28%)(P<0.05)。非耐药组1、2年累积生存率为77.14%和42.86%，明显高于耐药组 (54.12%和27.40%，P<0.05)。结论 原发性肝癌组织中MDR1编码产物P-gp异常过表达与肿瘤化疗耐药性相关，提示其可作为临床术后化疗用药的指导标志之一。
ABSTRACT: Objective To explore the relationship of MDR1 and its encoded product P-gp expressions with clinical efficacy of transcatheter arterial chemoembolization (TACE) in primary liver cancer and their clinical significance. Methods We selected 108 patients with primary liver cancer who came to our hospital between June 2010 and June 2013 as observation subjects. Meanwhile 50 healthy people in our hospital for liver biopsy were selected as controls. MDR1 mRNA level in observation group and control group was determined by real-time quantitative PCR. P-gp protein level was analyzed by immunohistochemistry. According to P-gp level, the 108 patients were divided into drug-resistance groups and non-resistance group; the relationship between P-gp expression level and clinical efficacy was analyzed. Results MDR1 mRNA level in liver tissues significantly enhanced in observation group compared with that in control group (P<0.05). In observation group 32 patients had the ratio of MDR1 mRNA level-normal level of more than 2 and 76 patients had the ratio of MDR1 mRNA level-normal level of less than 2. Immunohistochemistry revealed that MDR1 encoded product P-gp was brownish yellow, mainly expressed in the cell surface of liver cancer cells. There were 35 P-gp protein-negative patients (non-resistance group) and 73 positive patients (resistance group). Clinical efficacy was significantly higher in non-resistance group (74.28%) than in resistance group (43.28%) (P<0.05). The 1 year and 2-year cumulative survival rates were 54.12% and 27.40% in resistance group and 77.14% and 42.86%% in non-resistance group. They were significantly higher in the latter group (P<0.05). Conclusion The overexpressed MDR1 encoded product P-gp in primary liver cancer is associated with multidrug resistance in tumor chemotherapy, suggesting that P-gp can be used as one of the guiding clinical markers of