title: Identification of flotillin-1 as a novel biomarker for lymph node metastasis and prognosis of lung adenocarcinoma by quantitative plasma membrane proteome analysis.
abstract: 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.
authors.affiliation: Key Laboratory of Cancer Proteomics of Chinese Ministry of Health, Xiangya Hospital, Central South University, Changsha 410008, China.
authors.forename: Peng-Fei
authors.initials: PF
authors.lastname: Zhang
authors.forename: Gu-Qing
authors.initials: GQ
authors.lastname: Zeng
authors.forename: Rong
authors.initials: R
authors.lastname: Hu
authors.forename: Cui
authors.initials: C
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Yi
authors.forename: Mao-Yu
authors.initials: MY
authors.lastname: Li
authors.forename: Xin-Hui
authors.initials: XH
authors.lastname: Li
authors.forename: Jia-Quan
authors.initials: JQ
authors.lastname: Qu
authors.forename: Xun-Xun
authors.initials: XX
authors.lastname: Wan
authors.forename: Qiu-Yan
authors.initials: QY
authors.lastname: He
authors.forename: Jian-Huang
authors.initials: JH
authors.lastname: Li
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.forename: Xu
authors.initials: X
authors.lastname: Ye
authors.forename: Jiao-Yang
authors.initials: JY
authors.lastname: Li
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Wang
authors.forename: Xue-Ping
authors.initials: XP
authors.lastname: Feng
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Xiao
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D000328:Adult; D002462:Cell Membrane / Q000378:metabolism / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D020543:Proteome / Q000096:biosynthesis*; D040901:Proteomics / Q000379:methods; D015996:Survival Rate; D015854:Up-Regulation
chemical_list: D008565:Membrane Proteins; D009363:Neoplasm Proteins; D020543:Proteome; C106354:flotillins