非小细胞肺癌端粒酶活性与端粒酶RNA、端粒酶催化亚单位的相关性及其意义

目的 探讨非小细胞肺癌（non-small cell lung cancer,NSCLC)端粒酶活性（telomerase activity,TA)、端粒酶RNA（telomerase RNA，hTR）端粒酶催化亚单位（telomerase catalytic subunit,hTRT/hEST2)编码基因的表达，彼此间相关性及其预后意义。方法 TRAP－PCR（telomerase repeat amplification protocol PCR)检测TA，RT－PCR检测hTR，原位杂交检测hTRT/hEST2mRNA表达。结果 非小细胞肺癌TA、hTR和hTRT/hEST2 mRNA阳性率分别为68．4％（26／38）、55．2％（32／58）和74．1％（43／58），TA与hTRT/hEST2阳性相关（r=0.84,P=0.01),与hTR无相关性（r=0.16,P=0.23）。低分化以及有淋巴结或远处转移者TA及hTRT/hEST2阳性率增高；TA及hTRT/hEST2阳性组中位生存期（10．4个月，7．5个月）低于阴性组（13．5个月，14．7个月；P＝0．074，P＝0．01），hTR阳性组中位生存期（12．9个月）略高于阴性组（11．5个月，P＝0．23），仅hTRT/hEST2阳性与阴性组生存期差异有显著性；多因素Cox回归分析hTRT/hEST2对生存期有影响。结论 非小细胞肺癌TA、hEST2阳性与阴性组生存期差异有显著性；多因素Cox回归分析hTRT/hEST2对生存期有影响。结论 非小细胞肺癌TA、hTR和hTRT/hEST2表达高于癌旁正常组织；hTRT/hEST2够能反应TA活性，二者为NSCLC恶性表型增高的标志；hTRT/hEST2具有独立的预后意义。

Relationship among telomerase activity, telomerase RNA and telomerase catalytic subunit gene expression and their significance in non small-cell lung cancer.

Objective To study telomerase activity(TA), telomerase RNA(hTR) and telomerase catalystic subunit (hTRT/hEST 2) code gene expression in non small cell lung cancer (NSCLC), their relationship and significance. Methods Telomerase repeat amplification protocol PCR(TRAP PCR) for TA, RT PCR for hTR and in situ hybridization for hTRT/hEST 2 mRNA expression were performed. Results Positive rates of TA, hTR and hTRT/hEST 2 were 68.4%(26/38), 51.7%(32/58) and 74.2%(43/58) in NSCLC. But, the adjacent and benign lung tissues were negative for expression of TA, hTR and hTRT/hEST 2. A statistically significant positive correlation between TA and hTRT/hEST 2 was observed( r =0.84, P =0.01), though there was no statistically significant positive association between TA and hTR ( r =0.16, P =0.23). The median survivals of TA and hTRT/hEST 2 positive groups (10.4 months,7.5 months) were shorter than the negative ones (13.5 months,14.7 months). However, only the hTRT/hEST 2 group was found to show statistical significance to be an independent prognostic factor by multivariate Cox regression analysis. Conclusion Telomerase activity, hTR expression and hTRT/hEST 2 are frequently detected at higher levels in NSCLC than the pericancerous normal tissues. There is a positive correlation between TA and hTRT/hEST 2, both of which are markers of poor magnificent phenotype of NSCLC. The hTRT/hEST 2 has an independent prognostic significance.