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目的 探索组织蛋白酶D(CTSD)在肺腺癌发生发展中的表达特点及其意义.方法 使用氨基甲酸乙酯腹腔注射建立BALB/c小鼠肺腺癌模型;蛋白质组放射性核素相对标记和绝对定量(iTRAQ)分析筛选差异表达蛋白;免疫组织化学和Western blotting检测蛋白在肺腺癌不同病理时期的表达变化特点.结果 CTSD蛋白在肺腺癌早期表达较对照组明显增强;免疫组织化学和Western blotting检验分析发现,随着肺腺癌病程进展,CTD表达呈上升趋势,在肺腺癌晚期,实验组为对照组13.7倍;出现肝转移实验组小鼠肺组织CTSD呈现不同异构体.结论 CTSD是肺组织癌变过程中的重要蛋白,其异常表达和修饰可能在肺腺癌发生、发展和转移中起重要作用,可能成为肺腺癌早期诊断的分子指标.“,”Objective To investigate the expression characteristics and significance of cathepsin D(CTSD) in the initiation and progression of mouse lung adenocarcinoma.Methods We used urethane intraperitoneal injection to establish lung adenocarcinoma model in the BALB/c mouse.Differentially expressed proteins were identified using isobaric tag for relative and absolute quantitation (iTRAQ)-based quantitative proteomic technology in tumor group compared with control group.Cathepsin D expression characteristics were detected in different time points by immunohistochemical and Western blotting analysis.Results The expression of cathepsin D was significantly increased in the early-stage lung adenocarcinoma tissue compared with the control group.Immonohistochemical and Western blotting analysis observed that following tumor progression,cathepsin D expression was up-regulated.At the late-stage of lung adenocarcinoma,cathepsin D expression was 13.7-fold significantly higher than that in the control group and showed different molecular weight isoform of cathepsin D in the lung tissue of mouse with liver metastasis.Conclusion Cathepsin D is a critical protein in lung carcinogenesis.Aberrant expression and modification of cathepsin D may play an important role in the occurrence,development and metastasis of lung adenocarcinoma.Cathepsin D may have the potential to become biomarkers for early diagnosis of lung adenocarcinoma.