原发性肝癌多药耐药基因的表达与化疗敏感预测的相关性研究

Related research on the expressions of multi-drug resistance genes and chemosensitive prediction in primary liver cancer

目的探讨原发性肝癌多药耐药基因的表达与化疗敏感预测的相关性。方法取64例肝癌切除组织行ATP-TCA法肿瘤体外药敏试验,以RT-PCR法半定量检测肝癌多药耐药基因表达情况,分析多药耐药基因的表达与化疗敏感预测的相关性。结果1.原发性肝癌5种耐药基因的表达率分别为:MDR190.63%、MRP96.88%、GST-π96.88%、LRP90.63%、TOPOⅡ96.88%,各耐药基因的表达率间无显著相关。2.多药耐药基因MDR1、MRP、GST-п、LRP、TOPOⅡ的表达量在肝癌组织分别为1.17±0.47、1.59±0.33、1.18±0.48、1.03±0.48、1.00±0.31,在癌旁组织分别为1.11±0.38,1.32±0.44,1.04±0.42,0.96±0.32,1.19±0.28,除TOPOⅡ外,癌旁组耐药基因mRNA表达量低于肝癌组的表达量,两者间的差别无显著性(P>0.05)。3.多药耐药基因的表达与疗效的关系显示:在有效组中MDR1、MRP、GST-пLRPmRNA的表达量低于无效组,且在MDR1、MRP、LRP存在显著差别(P<0.05)。TOPOⅡmRNA的表达量有效组高于无效组,但差异无显著性(P>0.05)。4.ATP-TCA法肿瘤体外药敏试验临床敏感预测准确率为77.27%(17/22),对抗药性的预测准确率为100%(2/2);临床符合率为79.17%。5.MDR1的表达量与MIT、VP-16、EPI、TAX的IC50值正相关;MRP的表达量与MIT、VP-16、EPI的IC50值正相关;GST-π的表达量与5-FU、CDDP、OXA、GEM的IC50值正相关;LRP的表达量与5-FU、CDDP、OXA、EPI、GEM的IC50值正相关;TOPOⅡ的表达量与CPT的IC50值正相关。6.多药耐药基因预测化疗的准确率为72.70%。结论在肝癌存在实现化疗敏感预测基因化的可行性,可通过监测多药耐药基因的表达来预测化疗的效果,选择相关的化疗药物。

Objective To investigate the correlations of the expressions of multi-drug resistance genes and chemosensitive prediction in primary liver cancer. Methods The surgical and needle biopsy specimens of 64 patients were tested by the ATP-TCA. The expressions of adhesion molecules and MDR of tumor tissues of 64 cases and adjacent tissues of 12 cases of HCC were detected with RT-PCR. Results （1）The expression rates of MDR1, MRP, GST-π, LRP, TOPO Ⅱ mRNA was 90.63%, 96.88%, 96.88%, 90.63%, 96.88%, respectively, and there was no correlation among them. （2）The expression level of MDR1, MRP, GST-π, LRP, TOPOⅡ mRNA was 1.17±0.47, 1.59±0.33, 1.18±0.48, 1.03±0.48, 1.00±0.31 in liver cancer tissues respectively, was 1.11±0.38, 1.32±0.44, 1.04±0.42, 0.96±0.32, 1.19±0.28 in adjacent liver cancer tissues respectively,and there is no significant statistical difference between two groups. （3）In the group of chemotherapy response, the expression level of MDR1, MRP, GST-π, LRP mRNA were lower than that in the group of chemotherapy non-response, and showed a statistical difference in MDR1, MRP, LRP. the expression level of TOPO II mRNA in the group of chemotherapy response was higher than that in the group of chemotherapy non-response, but showed no statistical difference. （4） Predictive accuracy of drug chemosensitivity is 77.27% ,predictive accuracy of drug resistance is 100% ,predictive accuracy is 79.17%. （5）The expression level of MDR genes had positive Spearman correlations with the IC50 values of 10 kinds of anticancer agents. MDR1 had positive Spearman correlations with MIT, VP-16, EPI, TAX. MRP had positive Spearman correlations with MIT, VP- 16, EPI. GST-π had positive Spearman correlations with 5-FU, CDDP, OXA, GEM. LRP had positive Spearman correlations with 5-FU, CDDP, OXA, EPI, GEM. TOPO Ⅱ had positive Spearman correlation with CPT. （6）A Logistic regression was performed in the result of clinic evaluation and the expressions of MDR genes, a Logistic regression equation was obtained： Logit （P）=-11.789 ＋ 1.605X1＋6.428X2＋1.871X3-2.430X4＋0.693X5, the predictive accuracy of MDR was 72.70%. Conclusion It is possible to predict the chemosensitivity of HCC with genes in the future, the result of chemotherapy and the choose of anticancer agents can also be predicted by detecting the expression level of MDR.