Identification of Flotillin-1 as a novel biomarker for lymph node metastasis and prognosis of lung adenocarcinoma by quantitative plasma membrane proteome analysis

To identify a novel lung adenocarcinoma (AdC) biomarker, iTRAQ-tagging combined with 2D LC-MS/MS analysis was used to identify differentially expressed plasma membrane (PM) proteins in primary lung AdCs and paraneoplastic normal lung tissues (PNLTs). As a result, 36 differentially expressed membrane proteins were identified. Two differential PM proteins flotillin-1 and caveolin-1 were selectively validated by Western blotting. As there has been no report on the association of flotillin-1 with lung AdC, immunohistochemistry was further performed to detect the expression of flotillin-1 in the archival tissue specimens including 42 cases of PNLTs, 62 cases of primary lung AdCs with lymph node metastasis (LNM AdCs), and 46 cases of primary lung AdCs without lymph node metastasis (non-LNM AdCs), and the correlation of flotillin-1 expression levels in lung AdCs with clinicopathological features and clinical outcomes were evaluated. The results showed that up-regulation of flotillin-1 expression in lung AdCs was significantly correlated with advanced clinical stage, lymph node metastasis, increased postoperative relapse and decreased overall survival. Cox regression analysis revealed that the expressional level of flotillin-1 was an independent prognostic factor. The data suggest that flotillin-1 is a potential novel biomarker for lymph node metastasis and prognosis of lung AdC, and flotillin-1 up-regulation might play an important role in the pathogenesis of lung AdC.

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► We performed differential plasma membrane proteomic analysis in primary lung adenocarcinoma by iTRAQ and 2D LC-MS/MS.
► 36 differential membrane proteins were identified betwwen primary lung adenocarcinomas and their adjacent normal lung tissues.
► Two differential plasma membrane proteins flotillin-1 and caveolin-1 were validated by Western blot.
► Flotillin-1 expression is correlated with clinicopathologic characters of primary lung adenocarcinoma.
► Flotillin-1 is a potential novel biomarker for lymph node metastasis and prognosis of lung adenocarcinom.