Identification of integrin β1 as a prognostic biomarker for human lung adenocarcinoma using 2D-LC-MS/MS combined with iTRAQ technology

To discover novel lung adenocarcinoma (AdC) biomarkers, isobaric tags for relative and absolute quantitation (iTRAQ)-tagging combined with 2D-LC-MS/MS analysis was used to identify differentially expressed plasma membrane proteins in lung AdC and paired paraneoplastic normal lung tissues (PNLTs) adjacent to tumors. In this study, significant caveolin-1 downregulation and integrin beta 1 upregulation was observed in primary lung AdC vs. PNLT. As there has been no report on the association of integrin beta 1 with lung AdC, immunohistochemical staining was performed to detect the expression of integrin beta 1 in an independent set of archival tissue specimens including 42 cases of PLNT, 46 cases of without lymph node metastasis primary AdC (non-LNM AdC) and 62 cases of LNM AdC; the correlation of their expression levels with clinicopathological characteristics and clinical outcomes were evaluated. Based on the data, upregulation of integrin beta 1 was significantly correlated with advanced clinical stage and lymph node metastasis. Integrin beta 1 overexpression was significantly associated with advanced clinical stage (P<0.05), lymph node metastasis (P<0.05), increased relapse rate (P<0.05) and decreased overall survival (P<0.05) in AdCs. Cox regression analysis indicated that integrin beta 1 overexpression is an independent prognostic factor. The data suggest that integrin beta 1 is a potential biomarker for LNM and prognosis of AdC and integrin beta 1 upregulation may play an important role in the pathogenesis of AdC.