中文摘要：

为分析支气管上皮癌变进程中的差异表达蛋白质,筛选肺鳞癌早期诊断标志物,以人支气管上皮癌变各阶段组织为研究对象,先采用激光捕获显微切割技术（LCM）纯化人正常支气管上皮组织、鳞状化生、不典型增生、原位癌、浸润性肺鳞癌组织,再用同位素标记相对和绝对定量（iTRAQ）技术结合二维液相色谱串联质谱（2D LC-MS/MS）鉴定支气管上皮癌变进程中各阶段的差异表达蛋白质.结果共鉴定了1 036个蛋白质,筛选出102个与人支气管上皮癌变相关的差异蛋白质,在这些差异蛋白质中,有的在支气管上皮癌变过程中进行性上调,有的在支气管上皮癌变过程中进行性下调,有的呈阶段特异性改变.功能分析表明,这些差异蛋白质涉及代谢、细胞凋亡、增殖、分化、信号传导、转录、翻译、细胞黏附、免疫反应与发育等.Western blotting及免疫组织化学技术验证了其中2个差异蛋白（S100A9和CKB）的表达,证实了定量蛋白质组学结果的可靠性.研究结果提示：这些差异表达蛋白质与支气管上皮癌变相关,并可成为肺鳞癌的早期诊断标志物,进一步研究差异蛋白质的生物学功能,将有助于阐明支气管上皮的癌变机制,从而为肺鳞癌的早期诊断与发病机制研究提供新思路.

英文摘要：

To analyze the differentially expressed proteins in bronchial epithelial carcinogenesis process and discover novel biomarkers for early detection of human lung squamous cell cancer （LSCC）, iTRAQ-tagging combined with 2D LC-MS/MS analysis was used to identify differentially expressed proteins in human bronchial epithelial carcinogenic process using laser capture microdissection-purified normal bronchial epithelium （NBE）, squamous metaplasia （SM）, atypical hyperplasia （AH）, carcinoma in situ （CIS） and invasive LSCC. As a result, 1 036 proteins and 102 differentially expressed proteins were identified. Among these differentially expressed proteins, some proteins are progressively upregulated, some proteins are progressively downregulated in human bronchial epithelial carcinogenic process, and the other proteins are upregulated or downregulated in a certain stage of the process of carcinogenesis. Functional analysis and subcellular localization were performed on 102 differentially expressed proteins. Functional analysis showed that these differentially expressed proteins were associated with metabolic process, apoptosis, cell proliferation, cell differentiation, signal transduction, transcription, translation, cell adhesion, immune response, and development. Western blotting and immunohistochemistry were performed to detect the expression levels of the two proteins （S100A9 and CKB） in NBE, SM, AH, CIS and invasive LSCC, which also support the findings in MS analysis. The results suggest that these differentially expressed proteins associated with bronchial epithelial carcinogenesis, and they may be early diagnostic marker of lung squamous cell carcinoma. We further study the biological function of the differentially expressed proteins, will help to elucidate the bronchial epithelial carcinogenesis mechanism, and provide new ideas for early diagnosis and pathogenesis research of LSCC.