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Differential Proteomic Analysis Of Lung Squamous Cell Carcinoma And Lymph Node Metastasis

Posted on:2010-03-23Degree:DoctorType:Dissertation
Country:ChinaCandidate:F W TanFull Text:PDF
GTID:1264330401956129Subject:Clinical Medicine
Abstract/Summary:PDF Full Text Request
Lung cancer is one of the most frequent malignant tumors with vary high morbidity and mortality. Approximately,1200000people will be diagnosed with lung cancer all over the world per year. While lung cancer comprises only15%of new cancer diagnosis, it causes over30%of all cancer deaths. Developments in cancer research have been reported for recent decades, but lung cancer remains a very low5-year survival rate at15%all over the world and10%in china. So, more sensitive and effective techniques are required to overcome lung cancer. The proteins, which changed in expression level during cancer development and metastasis, are potential targets for cancer prognostication and therapy.Nowadays, proteomic approach is considered as a powerful technology in the global analysis of protein expression and has been widely used in disease research, especially in cancer research. Two-dimensional difference gel electrophoresis (2D-DIGE), which was considered as one of the major advances in proteomics development, is able to efficiently provide accurate and reproducible differential expression values for proteins in two or more biological samples. In this study, we employed2D-DIGE to analyze the differentially expressed proteins in tumor and adjacent normal tissue samples from12lung squamous carcinoma patients, then identified these differentially expressed proteins though MALDI-TOF/TOF mass spectrometry. Half of these12patients were proved with lymph node metastasis (LNM).In differential analysis between12tumors and paired normal tissues,66spots were significantly up-regulated (Ratio tumor/normal tissue≥2.0,p≤0.01) in tumor tissues while99spots were down-regulated (Ratio tumor/normal tissue≤-2, p≤0.01). Among these165differential spots,22up-regulated and19down-regulated proteins were identified by MALDI-TOF/TOF mass spectrometry. In differential analysis between6tumors with LNM and6tumors without LNM,24spots were significantly up-regulated (Ratio tumor with LNM/tumor without LNM≥1.5, p≤0.05) in tumors with LNM while20spots were down-regulated (Ratio mmor with LNM/tumor without LNM≤-1.5, p≤0.05). Among these44differential spots,8up-regulated and9down-regulated proteins were identified. According the information from Swiss-prot database, these identified differentially expressed proteins involve in cell skeleton formation, glycometabolism, redox regulation, protein transport, gene transcription, mRNA processing etc. Further studies for function of these differentially expressed proteins will contribute to discover the molecular mechanism and prognostication/therapy targets for lung squamous carcinoma. There were three proteins identified up-regulated in tumor tissue as well as LNM-related in our result. Therefore, they will be useful to prognosticate the LNM for lung squamous carcinoma as tissue biomarkers.
Keywords/Search Tags:Lung squamous carcinoma, Proteomics, 2D-DIGE, Mass spectrometry, MALDI-TOF/TOF
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