Identification of integrin ß1 as a prognostic biomarker for human lung adenocarcinoma using 2D-LC-MS/MS combined with iTRAQ technology.

ABSTRACT

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 ß1 upregulation was observed in primary lung AdC vs. PNLT. As there has been no report on the association of integrin ß1 with lung AdC, immunohistochemical staining was performed to detect the expression of integrin ß1 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 ß1 was significantly correlated with advanced clinical stage and lymph node metastasis. Integrin ß1 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 ß1 overexpression is an independent prognostic factor. The data suggest that integrin ß1 is a potential biomarker for LNM and prognosis of AdC and integrin ß1 upregulation may play an important role in the pathogenesis of AdC.