紫杉醇化疗后卵巢上皮性癌组织中COP9、JAK2、HSP、NADH基因表达的变化及其意义

Expression of COP9,JAK2,HSP and NADH in ovarian carcinoma tissues after taxol-chemotherapy and their significance

目的探讨卵巢上皮性癌（卵巢癌）紫杉醇化疗后癌组织中COP9、JAK2、HSP、NADH基因表达的变化及其意义。方法采用RT-PCR技术及实时定量PCR技术检测54份卵巢癌组织中JAK2、HSP、NADH和COP9基因的表达，并分析其临床意义。其中，接受紫杉醇化疗者33份（接受2—4、6—10个疗程化疗者分别为15、18份），未接受化疗者21份；病理分级：G1-G2 24份，G3，30份；病理类型：浆液性囊腺癌26份，黏液性囊腺癌21份，子宫内膜样腺癌7份；手术病理分期：Ⅲ期49份，Ⅳ期5份。结果RT-PCR技术检测显示，COP9基因过度表达率化疗者为39％，明显低于未化疗者的95％（P〈0．01）；而JAK2、HSP、NADH基因过度表达率化疗者分别为91％、97％及94％，明显高于未化疗者的29％、48％及43％（P〈0．05）。除JAK2基因过度表达率在不同病理分级的癌组织中比较，差异有统计学意义（P〈0．01）外，其他基因在不同病理分级、病理类型、手术病理分期及不同疗程化疗者间比较，差异均无统计学意义（P〉0．05）。进一步行实时定量PCR技术检测显示，化疗者COP9、JAK2、HSP和NADH基因的拷贝数分别为568、7653、5766和3200，未化疗者分别为1886、3094、3341和1522，两者分别比较，差异均有统计学意义（P〈0．05）。除COP9基因的拷贝数在不同疗程化疗患者的癌组织中比较，差异无统计学意义（P〉0．05）外，其他基因在不同疗程化疗、病理分级的癌组织中比较，差异均有统计学意义（P〈0．05）；上述4个基因拷贝数在不同病理类型间比较，差异均无统计学意义（P〉0．05）。Ⅳ期患者癌组织中HSP、NADH基因拷贝数明显高于Ⅲ期（P值分别为〈0．01、〈0．05）；但COP9及JAK2基因拷贝数在两者间比较，差异无统计学意义（P〉0．05）。JAK2、HSP、NADH基因表达3者间均呈明显正相关关系（r=0．56、0．44、0．57，P均〈0．01）；COP9与JAK2基因表达呈明显负相关关系（r=-0．48，P〈0．01），但与HSP、NADH基因表达无明显相关性（r=-0．18、-0．06，P均〉0．05）。结论COP9基因表达的下调和JAK2、HSP、NADH基因表达的上调可能与卵巢癌紫杉醇化疗耐药有一定的关系。

Objective To study the expression of COP9, JAK2, HSP and NADH genes in ovarian carcinoma tissues after taxol-chemotherapy and their significance. Methods The up-regulated genes of JAK2,HSP, NADH and the down-regulated gene of COP9, which were revealed by micro-array from our previous study were examined by RT-PCR and real-time-PCR in 33 cases of ovarian cancer who previously received taxol-based chemotherapy （ group 1 ）, and 21 cases of ovarian cancer who never received chemotherapy before operation （group 2 ）. Results The expression rate of COP9 gene in group 1 was detected markedly lower than that in group 2 （39% vs 95% , P 〈 0. 01 ） ; whereas the expression rates of JAK2, HSP and NADH in group 1 were significantly higher that those in group 2 （91%, 97%, 94% vs 29%, 48%, 43% ; all P〈0. 05）. And the expression of COP9, HSP and NADH genes had no significant differences among histological grades. However, a significantly higher expression of JAK2 gene was seen in grade 3 than in grade 1 - 2 （P 〈0.01 ）. No significant difference in the expression rates of the 4 genes was seen among various tumor types or chemotherapy courses （P 〉 0. 05 ）. Real-time PCR showed that the level of COP9 gene copies of group 1 was significantly lower than that of group 2 （568, 1866 respectively; P 〈 0. 05）. However,HSP, JAK2 and NADH genes had significantly higher copy numbers in group 1 than in group 2 （5766,7653,3200 in group 1 and 3341,3094,1522 in group 2, respectively ; all P 〈 0. 05）. In the subgroup that received 6 - 10 chemotherapy courses, the copy concentrations of JAK2, HSP, NADH genes were higher than those in the subgroup that received 2 -4 chemotherapy courses （all P 〈 0. 05 ）. In addition, we found a higher copy concentrations of JAK2, HSP, NADH genes in grade 3 than in grade 1 -2 （all P 〈 0. 05 ）. Though no significant differences in gene copy concentrations of the 4 genes were seen among variable tumor types. In stage IV, the copy concentrations of HSP and NADH genes were higher than those in stage Ⅲ（ P 〈 0. 01, P 〈 0. 05 respectively ） , but the copy concentrations of COP9, JAK2 genes had no significant differences （both P 〉 0. 05 ）. There were positive correlations among JAK2, HSP and NADH genes （ r =0. 56,0.44,0. 57 respectively ,all P 〈0. 01 ）. COP9 gene was found to have a negative correlation with JAK2 gene （ r = - 0.48 ; P 〈 0. 01 ）, but not with HSP and NADH genes （ r = - 0. 18, - 0. 06, respectively ; both P 〉 0.05 ）. Conclusion The down-regulation of COP9 gene and up-regulation of JAK2, HSP, and NADH genes are related to the mechanism of drug-resistance in ovarian cancer.