组织蛋白酶D新的糖基化异构体在肺癌中表达的临床意义及其与预后的相关性

目的 探讨组织蛋白酶D（CTSD）新的糖基化异构体与肺癌临床病理特征及预后的相关性。 方法 应用免疫组织化学和半定量RT PCR方法检测119例肺癌组织和39例癌旁组织中CTSD的表达；Western blotting分析CTSD各异构体表达特点；去糖基化实验检测CTSD 蛋白的糖基化修饰；Kaplan-Meier分析66kD异构体、临床病理资料与肺癌术后整体生存期的相关性。 结果 CTSD在肺鳞癌、腺癌和小细胞肺癌组织中高表达；66kD蛋白为CTSD新的糖基化异构体，该异构体表达与肺癌组织类型、临床分期、淋巴结转移和患者的吸烟史密切相关（P<0.05），阳性表达和阴性表达患者术后中位生存时间分别为20.0和30.0个月（P<0.05）；肺癌组织类型、临床分期、淋巴结转移、肿瘤大小和66kD异构体表达是影响肺癌预后的独立因素。 结论 CTSD 66kD异构体阳性表达可能是肺癌预后不良的分子标志物之一。

Clinical significance and correlation with prognosis of novel glycosylation isoform of cathepsin D expression in lung cancer

Objective To study the correlation of novel glycosylation isoform of cathepsin D (CTSD) expression with clinical features and its prognostic value in lung cancer. Methods Immunohistochemistry and Semi-quantitative RT-PCR were used to examine the cathepsin D expression, and Western blotting to analyze characterization of cathepsin D isoforms expression in 119 lung cancer tissues and 39 paraneoplastic tissues. Deglycosylation experiment was performed to check glycosylation-modified condition of cathepsin D. The association of 66kD isoform expression with clinical features and lung cancer prognosis was determined by Kaplan-Meier survival analysis. Results Cathepsin D highly expressed in squamous carcinomas, adenocarcinoma and small cell carcinoma tissues. 66kD protein form of cathepsin D was a novel glycosylation isoform of cathepsin D, its expression was associated with lung cancer histological type, clinical stage, lymph node metastasis and smoking status(P<0.05). The median survival time of lung cancer with 66kD isoform positive and negative expression were 20.0 months and 30.0 months, respectively (P<0.05). Histological type, clinical stage, lymph node metastasis, tumor size and 66kD isoform were independent prognostic factor of lung cancer. Conclusion Positive expression of 66kD isoform of cathepsin D may be one of molecular markers which correlate with poor prognosis of lung cancer.