晚期鼻咽癌患者基因治疗前后TS和GST-π及TopoⅡ的表达变化及其与预后的关系

The expression of TS,GST-π,TopoⅡ in advanced nasopharyngeal carcinoma patients treated with gene therapy and its influence on prognosis

目的初步探讨重组人p53腺病毒(rAd-p53)鼻咽部瘤内注射前后的鼻咽癌原发灶中胸苷酸合成酶(TS)、谷胱甘肽S-转移酶π(GST-π)和拓扑异构酶Ⅱ(TopoⅡ)的表达变化及其临床意义。方法采用免疫组化法检测80例晚期鼻咽癌患者治疗前后肿瘤组织中TS、GST-π和TopoⅡ的表达情况。结果常规放化疗组在治疗后其TS、GST-π和TopoⅡ的表达明显升高(P分别为0.01、0.01、0.00),基因治疗组和单纯放疗组其治疗后TS、GST-π和TopoⅡ的表达未见明显改变(P>0.05)。三组间的复发率和转移率差异无统计学意义(P=0.95)。疗前GST-π阴性患者其复发率和转移率明显低于阳性患者(8.93%vs54.17%,P=0.00)。结论 GST-π蛋白的异常表达与晚期鼻咽癌治疗后复发转移有关。基因治疗晚期鼻咽癌可能通过抑制TS、GST-π、TopoⅡ蛋白表达进而逆转鼻咽癌化疗耐药。

Objective To investigate the expression of thymidylate synthase （TS）, glutathione S-transferase enzyme π（GST-π） and topoisomerase Ⅱ（Topo Ⅱ ） protein before and after the recombinant human p53 adenovirus （rAd-p53） intratumoral injection and its significance. Methods Eighty patients with advanced nasopharyngeal carci- noma were randomly divided into 3 groups：the gene therapy group （30 cases） ： rAd-p53 intratumoral injection and concurrent chemo-radiotherapy, the conventional chemoradiotherapy group （30 cases） and the radiotherapy group （20 cases）. Clinical data and the nasopharyngeal tumor tissues which were intratumoral injection with rAd-p53 were collected. The two-step immunohistochemical was done to detect the TS, GST-π and Topo Ⅱ protein expression in the primary tumor tissue of nasopharyngeal carcinoma. Results The expression TS, GST-π and Topo Ⅱ in conven- tional chemoradiotherapy group was significantly higher than that before treatment （P values were 0. 01,0. 01,0. 00）. In gene treatment group, the expression TS, GST-π and Topo Ⅱ did not change significantly （P 〉 0. 05）. There were no significant difference in the expression of TS, GST-π and TopoⅡ before and after radiotherapy alone（ P 〉 0. 05 ）. Among the three groups, the recurrence rate and metastasis rate were not significantly different （ P = 0. 95 ）. The re- currence rate in GST-π negative patients was significantly lower than that in positive patients （8.93% vs. 54. 17%, P = 0. 00）. Conclusion GST-π protein expression is positively correlated with recurrence and metastasis in patients with advanced nasopharyngeal carcinoma after treatment. The rAd-p53 intratumoral injection can reverse chemo- resistance of nasopharyngeal carcinoma by inhibition of GST-π, Topo Ⅱ protein, which might be its mechanism of NPC treatment.