多药耐药相关蛋白2、3与原发性肝癌合并门静脉癌栓术后辅助化疗疗效的相关性研究

doi:10.3877/cma.j.issn.1674-0793.2014.05.009

中华普通外科学文献(电子版) ›› 2014, Vol. 08 ›› Issue (05) : 376 -380. doi: 10.3877/cma.j.issn.1674-0793.2014.05.009

所属专题：文献；

论著

多药耐药相关蛋白2、3与原发性肝癌合并门静脉癌栓术后辅助化疗疗效的相关性研究

胡文杰¹, 黎东明¹, 陈伟¹, 张昆松¹, 黄力¹, 梁力建¹^,^†(

)

^1. 510080　广州，中山大学附属第一医院肝胆外科

收稿日期:2014-08-18 出版日期:2014-10-01
通信作者: 梁力建
基金资助:
广东省自然科学基金资助项目(S2013010015386)

Study on the correlation between the expression of MRP2 and MRP3 and efficacy of chemotherapy in hepatocellular carcinoma patients with tumor thrombi in major portal vein

Wenjie Hu¹, Dongming Li¹, Wei Chen¹, Kunsong Zhang¹, Li Huang¹, Lijian Liang¹^,^†()

^1. Department of Hepatobiliary Surgery, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China

Received:2014-08-18 Published:2014-10-01
Corresponding author: Lijian Liang
About author:
Corresponding author: Liang Lijian, Email: lianglj@medmail.com.cn

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目的

研究多药耐药相关蛋白2、3（MRP2、MRP3）表达与原发性肝细胞癌（HCC）合并门静脉癌栓患者术后辅助化疗疗效的相关性。

方法

收集2001年1月至2005年12月术后接受化疗的29例HCC合并门静脉癌栓患者的石蜡标本，构建组织芯片。采用免疫组织化学染色技术检测MRP2、MRP3的表达情况。将蛋白表达强度（++）以上设为耐药组，其余为非耐药组，结合临床资料进行生存分析。

结果

MRP2、MRP3阳性表达率分别为86.21％（25/29）和62.07％（18/29）。依据MRP2表达情况，耐药组19例和非耐药组10例进行生存分析显示，总体生存期（P=0.010）及无瘤生存期（P=0.039）差异有统计学意义。依据MRP3表达情况，耐药组16例和非耐药组13例比较，仅无瘤生存期差异有统计学意义（P=0.043）。多因素Cox回归分析显示，MRP2（P=0.009，HR=4.897，95% CI=1.475~16.261）、MRP3（P=0.002，HR=5.515，95% CI=1.861~16.341）表达情况为无瘤生存的独立影响因子。

结论

MRP2、MRP3的强表达是导致肝癌耐药及化疗效果欠佳的原因之一。MRP2、MRP3有可能作为原发性肝癌患者临床筛选化疗方案的指标。

关键词: 多药耐药相关蛋白, 肝细胞癌, 癌栓, 门静脉, 化疗

Objective

To investigate the expression of multidrug resistance- associated proteins (MRP2, MRP3) and their correlation to chemotherapeutic efficacy in hepatocellular carcinoma (HCC) with tumor thrombi in major portal vein.

Methods

Twenty-nine HCC patients with tumor thrombi in major portal vein following hepatectomy, thrombectomy and postoperative adjuvantchemotherapy were enrolled in this study. Specimens embedded in paraffin were collected for the construction of tissue microarrays. MRP2 and MRP3 were visualized by immunohistochemical staining. The patients were divided into chemotherapy sensitive and resistant groups according to the staining grade. The intensity≥(++) were considered resistant to chemotherapy. Survival time was compared between the two groups and prognostic factors were identified using Cox proportional hazards model.

Results

The positive rate of MRP2 and MRP3 was 86.21%, 62.07% , respectively. Tumor-free survival time and overall survival time were significantly different between the two groups according to the staining grade of MRP2 (P=0.039, 0.010, respectively). Only tumor-free survival time was significantly different according to the staining grade of MRP3 (P=0.043). Multivariate analysis revealed that the expression grade of MRP2 and MRP3 was independent prognostic factor for tumor-free survival time (P=0.009, 0.002, respectively).

Conculsion

In HCC patients with tumor thrombi in major portal vein, the overexpression of MRP2, MRP3 is one of the major reasons for resistance to chemotherapy. Detection of MRP2 and MRP3 will be helpful in chemotherapy decision making.

Key words: Multidrug resistance-associated protein, Hepatocellular carcinoma, Tumor thrombi, Portal vein, Chemotherapy

图1 MRP2阳性表达，胞膜/胞质可见棕黄色染色颗粒（免疫组化染色×400）

图2 MRP3阳性表达，胞膜/胞质可见棕黄色染色颗粒（免疫组化染色×400）

图3 两组患者的总体生存曲线，按MRP2表达分组，绿色曲线为耐药组，蓝色曲线为非耐药组，两组比较，P=0.010

图4 两组患者的无瘤生存曲线，按MRP2表达分组，绿色曲线为耐药组，蓝色曲线为非耐药组，两组比较，P=0.039

图5 两组患者的无瘤生存曲线，按MRP3表达分组，绿色曲线为耐药组，蓝色曲线为非耐药组，两组比较，P=0.043

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