title: Early Candidate Biomarkers of Non-Small Cell Lung Cancer Are Screened and Identified in Premalignant Lung Lesions.
abstract: A specific protein profile that accompanies neoplastic transformation in the premalignant airway epithelium could provide an opportunity for early diagnosis of lung cancer. The aim of this study was to screen and identify early candidate biomarkers of non-small cell lung cancer. Thirteen non-small cell lung cancer samples were obtained within 30 minutes after a surgical resection. Laser capture microdissection was performed to enrich the normal lung cell and squamous metaplasia or atypical adenomatous hyperplasia cell populations. The resulting tandem mass spectrum was automatically searched for proteins against International Protein Index (IPI) human protein database using the TurboSEQUEST searching engine. The molecular function and biological processes of identified proteins were determined based on universal bioinformatics tools. The 2 proteins of interest, focal adhesion kinase and C-terminal Src kinase, were validated using Western blot method. A total of 863 proteins were identified by automatically searching the tandem mass spectrum, among which 427 were dysregulated expression in premalignant airway epithelium compared with those of normal lung cells. The 427 proteins were mainly distributed in 24 sorts of cellular components, 22 molecular function, 15 biological processes, and 10 significant perturbations of pathways. The most significant network included 48 genes and was related to energy production, cell cytoskeleton, cell adhesion, metabolism, oxidative stress, and small molecule biochemistry. Focal adhesion kinase and C-terminal Src kinase were significantly overexpressed in premalignant lung lesion cells compared with the normal lung cells in 13 cases. We identified that there were 427 proteins involved in non-small cell lung cancer carcinogenic process and confirmed the key biological pathways in premalignant lung tissue. The significantly upregulated focal adhesion kinase and C-terminal Src kinase could be considered as molecular biomarkers for early diagnosis and prognosis of non-small cell lung cancer.
authors.affiliation: 1 Department of Respiratory Medicine, Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Yandong
authors.initials: Y
authors.lastname: Nan
authors.affiliation: 2 Department of Health Examination Center, Shaanxi Province People's Hospital, Xi'an, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Du
authors.affiliation: 3 Department of Respiration, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Lijie
authors.initials: L
authors.lastname: Ma
authors.affiliation: 3 Department of Respiration, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Jiang
authors.affiliation: 3 Department of Respiration, Tangdu Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Faguang
authors.initials: F
authors.lastname: Jin
authors.affiliation: 1 Department of Respiratory Medicine, Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Shuanying
authors.initials: S
authors.lastname: Yang
mesh_terms: D014408:Biomarkers, Tumor; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000378:metabolism*; D019295:Computational Biology / Q000379:methods; D055088:Early Detection of Cancer; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000378:metabolism*; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011230:Precancerous Conditions / Q000175:diagnosis* / Q000378:metabolism*; D040901:Proteomics / Q000379:methods
chemical_list: D014408:Biomarkers, Tumor
keywords: C-Src; FAK; NSCLC; biomarkers; early diagnosis; proteomics
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