肝癌多药耐药基因表达的临床研究

A study on the expression of MDR1 mRNA in human hepatocellular carcinoma

目的 探讨肝癌多药耐药基因 (MDR1)mRNA表达与癌分化、临床病理学特征、化疗效果、转移复发及预后的关系。方法 收集肝癌组织及癌旁 2cm肝组织 4 7例 ,正常肝组织 12例 ,采用荧光定量RT PCR方法检测MDR1mRNA的表达。结果 MDR1mRNA表达强度在 1 4× 10 3 ～3 6× 10 6copy/ μgRNA ,癌组织阳性率为 72 % ,明显高于癌旁肝组织 (5 1% )和正常肝组织 (4 2 % )(P <0 0 5 )。癌组织MDR1mRNA表达与癌灶直径、有无转移、Okuda分期、癌结节数目呈正相关 ,与复发时间、有无包膜及患者的生存期呈负相关关系。回归分析表明MDR1mRNA主要与癌灶转移潜能有关 (B =1 82 3,OR =6 187,P <0 0 5 )。MDR1mRNA阳性组化疗与疗效间无相关性 ,而MDR1mRNA阴性组术后局部化疗能明显改善肝癌的疗效 (r =0 773,P <0 0 5 ) ,其生存曲线明显高于MDR1mRNA阳性组。结论 MDR1mRNA基因表达与肝癌原发性耐药及癌灶转移潜能有关。

Objective To investigate MDR1mRNA quantitative expression in patients with hepatocellular carcinoma( HCC) and its relation to pathologic features, chemotherapy sensitivity, metastasis and prognosis. Methods Total RNA extracted from 47 cases of HCC and 12 normal liver tissue were subjected to analysis of MDR1mRNA expression by fluoregenic probe quantitative RT-PCR(FQ-RT-PCR). Result The level of MDR1mRNA expression was 1.4×10 3～3.6×10 6copies/μg RNA .The positive rates observed in 72% of the tumor tissue was significantiy higher than in 51% of the adjacent liver tissue and in 42% of the normal liver tissue (P<0.05). The level of MDR1mRNA of HCC was in positive correlation with tumor size, Okuda′s stage, tumor nodules, metastasis and negative correlation with recurrence, survival time and tumor encapsulation(all P<0.05). Expression of MDR1mRNA of HCC had significant association with metastasis by Logstic regression. The chemotherapy sensitivity were significantly correlated with the expression of MDR1mRNA in HCC. Kaplam-meier survival analysis showed that median actuarial survival was longer in negative MDR1mRNA group than in positive group (P<0.01). Conclusion The expression of MDR1mRNA was correlated with HCC sensitivity to chemotherapy and metastasis.