切换至 "中华医学电子期刊资源库"

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. 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. 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:
引用本文:

胡文杰, 黎东明, 陈伟, 张昆松, 黄力, 梁力建. 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[J/OL]. 中华普通外科学文献(电子版), 2014, 08(05): 376-380.

Wenjie Hu, Dongming Li, Wei Chen, Kunsong Zhang, Li Huang, Lijian Liang. 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[J/OL]. Chinese Archives of General Surgery(Electronic Edition), 2014, 08(05): 376-380.

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。

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.

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
[1]
Liver Cancer Study Group of Japan. Primary liver cancer in Japan. Clinicopathologic features and results of surgical treatment[J]. Ann Surg, 1990, 211(3): 277-287.
[2]
Fujii T,Takayasu K,Muramatsu Y, et al. Hepatocellular carcinoma with portal tumor thrombus: analysis of factors determining prognosis[J]. Jpn J Clin Oncol, 1993, 23(2): 105-109.
[3]
Ikai I,Arii S,Ichida T, et al. Report of the 16th follow-up survey of primary liver cancer[J]. Hepatol Res, 2005, 32(3): 163-172.
[4]
Llovet JM,Bustamante J,Castells A, et al. Natural history of untreated nonsurgical hepatocellular carcinoma: rationale for the design and evaluation of therapeutic trials[J]. Hepatology, 1999, 29(1): 62-67.
[5]
Nies AT,Konig J,Pfannschmidt M, et al. Expression of the multidrug resistance proteins MRP2 and MRP3 in human hepatocellular carcinoma[J]. Int J Cancer, 2001, 94(4): 492-499.
[6]
胡文杰,黎东明,陈伟, 等. P-糖蛋白表达与原发性肝癌合并门静脉癌栓患者术后辅助化疗效果的相关性研究[J/CD]. 中华普通外科学文献:电子版, 2013, 7(5): 350-353.
[7]
Cole SP,Bhardwaj G,Gerlach JH, et al. Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line[J]. Science, 1992, 258(5088): 1650-1654.
[8]
Breuninger LM,Paul S,Gaughan K, et al. Expression of multidrug resistance-associated protein in NIH/3T3 cells confers multidrug resistance associated with increased drug efflux and altered intracellular drug distribution[J]. Cancer Res, 1995, 55(22): 5342-5347.
[9]
Nooter K,Westerman AM,Flens MJ, et al. Expression of the multidrug resistance-associated protein (MRP) gene in human cancers[J]. Clin Cancer Res,1995, 1(11): 1301-1310.
[10]
Korita PV,Wakai T,Shirai Y, et al. Multidrug resistance-associated protein 2 determines the efficacy of cisplatin in patients with hepatocellular carcinoma[J]. Oncol Rep, 2010, 23(4): 965-972.
[11]
Bonin S1,Pascolo L,Crocé LS, et al. Gene expression of ABC proteins in hepatocellular carcinoma, perineoplastic tissue, and liver diseases[J]. Mol Med, 2002, 8(6): 318-325.
[1] 史学兵, 谢迎东, 谢霓, 徐超丽, 杨斌, 孙帼. 声辐射力弹性成像对不可切除肝细胞癌门静脉癌栓患者放射治疗效果的评价[J/OL]. 中华医学超声杂志(电子版), 2024, 21(08): 778-784.
[2] 洪玮, 叶细容, 刘枝红, 杨银凤, 吕志红. 超声影像组学联合临床病理特征预测乳腺癌新辅助化疗完全病理缓解的价值[J/OL]. 中华医学超声杂志(电子版), 2024, 21(06): 571-579.
[3] 王卫东. 贲门周围血管离断与左膈下静脉的保留[J/OL]. 中华普通外科学文献(电子版), 2024, 18(06): 464-464.
[4] 常小伟, 蔡瑜, 赵志勇, 张伟. 高强度聚焦超声消融术联合肝动脉化疗栓塞术治疗原发性肝细胞癌的效果及安全性分析[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 56-59.
[5] 李代勤, 刘佩杰. 动态增强磁共振评估中晚期低位直肠癌同步放化疗后疗效及预后的价值[J/OL]. 中华普外科手术学杂志(电子版), 2025, 19(01): 100-103.
[6] 许杰, 李亚俊, 冯义文. SOX新辅助化疗后腹腔镜胃癌D2根治术与常规根治术治疗进展期胃癌的近期随访比较[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(06): 647-650.
[7] 薛庆, 施赛叶, 徐雅文, 盛夏, 张芹芹. 追踪方法学联合失效模式与效应分析在膀胱灌注化疗患者中的应用[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2024, 18(06): 553-559.
[8] 张昊, 潘卫东. 胰腺癌新辅助化疗后可切除性评估现状及进展[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(05): 629-633.
[9] 赵磊, 刘文志, 林峰, 于剑, 孙铭骏, 崔佑刚, 张旭, 衣宇鹏, 于宝胜, 冯宁. 深部热疗在改善结直肠癌术后辅助化疗副反应及生活质量中的作用研究[J/OL]. 中华结直肠疾病电子杂志, 2024, 13(06): 488-493.
[10] 韩加刚, 王振军. 梗阻性左半结肠癌的治疗策略[J/OL]. 中华结直肠疾病电子杂志, 2024, 13(06): 450-458.
[11] 石阳, 于剑锋, 曹可, 翟志伟, 叶春祥, 王振军, 韩加刚. 可扩张金属支架置入联合新辅助化疗治疗完全梗阻性左半结肠癌围手术期并发症分析[J/OL]. 中华结直肠疾病电子杂志, 2024, 13(06): 464-471.
[12] 梁轩豪, 李小荣, 李亮, 林昌伟. 肠梗阻支架置入术联合新辅助化疗治疗结直肠癌急性肠梗阻的疗效及其预后的Meta 分析[J/OL]. 中华结直肠疾病电子杂志, 2024, 13(06): 472-482.
[13] 张颖, 赵鑫, 陈佳梅, 李雁. 术前化疗对CRS+HIPEC 治疗腹膜假黏液瘤预后影响的meta 分析[J/OL]. 中华临床医师杂志(电子版), 2024, 18(09): 826-835.
[14] 蔡晓雯, 李慧景, 丘婕, 杨翼帆, 吴素贤, 林玉彤, 何秋娜. 肝癌患者肝动脉化疗栓塞术后疼痛风险预测模型的构建及验证[J/OL]. 中华临床医师杂志(电子版), 2024, 18(08): 722-728.
[15] 王子阳, 王宏宾, 刘晓旌. 血清标志物对甲胎蛋白阴性肝细胞癌诊断的研究进展[J/OL]. 中华临床医师杂志(电子版), 2024, 18(07): 677-681.
阅读次数
全文


摘要