肝细胞癌肺耐药蛋白基因的表达及临床意义

The expression of lung resistance protein gene (LRP) in hepatocellular carcinoma (HCC) and its clinical significance

目的研究肺耐药蛋白 (lungresistance protein ,LRP)基因LRP在肝细胞癌(hepatocellularcarcinoma ,HCC)中产生的多药耐药机制 ,及其与预后的关系。方法采用SP免疫组织化学法和原位PCR技术对 5 4例未化疗的HCC ,2 4例癌旁和 12例肝炎后肝硬化组织中LRP编码的LRP和mRNAlrp的表达进行检测 ,对术后 2 4例AFP阳性的HCC患者进行术后化疗 ,分析LRP表达与AFP变化关系。结果LRP和mRNAlrp在 3种组织中的阳性表达率分别为 6 1%、33%、17%和 76 %、38%、33%。HCC组织中LRP表达显著高于其他组织 (CMH统计量为 9 32 ,10 96 ,P值均小于 0 0 1)。LRP表达与HCC的分化程度有关 (CMH统计量为 4 2 7,6 71,P值分别小于 0 0 5、0 0 1)。LRP ,mRNAlrp表达阳性组患者术后化疗AFP下降率 [有效率分别为 2 0 % (3/ 15 ) ,2 5 % (4 /16 ) ],显著低于LRP及mRNAlrp表达阴性组 [有效率分别为 78% (7/ 9)及 88% (7/ 8) (P值分别小于 0 0 5、0 0 1) ]。术后随访mRNAlrp表达阳性组患者术后平均生存为 (36± 10 )个月 ,而阴性组为(4 5± 11)个月 (t=2 6 76 0 ,P <0 0 1)。结论HCC化疗多药耐药与其LRP表达有关 ,LRP表达也与HCC的分化程度有关 ,检测LRP表达对预测化疗耐药具有指导意义。

ObjectiveTo study the multidrug resistance (MDR) produced by lung resistance protein gene (LRP) in HCC, and the relationship between LRP and prognosis of HCC patients. Methods The expression of LRP encoding LRP and mRNA lrp was examined in the cancer tissue of 54 cases of previously untreated HCC, cancer adjacent liver tissue and liver biopsy of posthepatitic cirrhosis in 12 cases. The relationship between the expression of LRP and the change of AFP level in 24 posthepatectomy HCC cases was observed after receiving postoperative adjuvant chemotherapy in which the AFP had been positive. Results The positive rate of LRP and mRNA lrp was 61%, 33%, 17%, and 76%, 38%,33% respectively in three corresponding tissues, with significant difference between untreated HCC and two other tissues (CMH=4 27,6 71; P <0 05, P <0 01). The expression of LRP was correlated to the degree of HCC differentiation (CMH=4 27,6 71; P <0 05, P <0 01). Meanwhile, The postchemotherapy decrease of AFP 20%(3/15), 25%(4/16) in the group with positive expression of LRP and mRNA lrp was less than that of 78%(7/9), 88%(7/8) in LRP negative group ( P <0 05, P <0 01). The difference was significant in the postoperative mean survival time (45±11 mon vs. 36±10 mon) between negative mRNA lrp expression group and positive group ( t =2 676 0, P <0 01). Conclusions MDR of HCC is related to LRP expression, LRP gene expression correlates with differential degree of HCC. Detection of LRP expression could predict chemotherapy resistance of HCC.