Flotillin2 expression correlates with HER2 levels and poor prognosis in gastric cancer

PLoS One. 2013 May 2;8(5):e62365. doi: 10.1371/journal.pone.0062365. Print 2013.

Abstract

Objective: Flotillin gene is known as a tumor promoter or suppressor, depending on the tumor type or tumor stage. We aimed to investigate the clinical significance of flotillin2 protein expression in gastric cancer.

Methods: We examined flotillin2 and erbB2 levels in tissue microarray of 282 gastric cancer samples and analyzed the association between flotillin2 levels, clinicopathologic factors and prognosis. The regulation of erbB2 by flotillin2 was examined with flotillin2 siRNA-transfected gastric cancer cells.

Results: Flotillin2 partially co-localized with erbB2 at the plasma membrane as detected by confocal microscopy, levels of erbB2 were reduced after flotillin knockdown in SGC-7901 cancer cells, and the expression of flotillin2 was positively correlated with that of erbB2. In non-neoplastic gastric mucosa, flotillin2 was not expressed in the epithelial compartment. In gastric cancer, positive staining of flotillin2 was shown in 129 (45.7%) of 282 cases, also, it was significantly associated with a Lauren grade, histologic type, lymphovascular invasion and tumor location. Moreover, survival analysis showed that flotillin2 expression was an independent prognostic factor of poor survival (p<0.001).

Conclusions: These results indicate that a positive correlation exists between flotillin2 and erbB2 expression levels, flotillin2 maybe involved in the stabilization of erbB2 at the plasma membrane, flotillin2 is significantly correlated with cancer progression and poor prognosis in gastric cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Carcinogenesis
  • Cell Line, Tumor
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism*
  • Prognosis
  • Protein Transport
  • Proteolysis
  • Receptor, ErbB-2 / genetics*
  • Receptor, ErbB-2 / metabolism*
  • Stomach Neoplasms / diagnosis*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology

Substances

  • Membrane Proteins
  • flotillins
  • ERBB2 protein, human
  • Receptor, ErbB-2

Grants and funding

This work was supported by grants from the National Natural Science Foundation of China (81272718), Young Scholars' Research Fund for the Doctoral Program of Higher Education of China (20122104120008) and Fund for Scientific Research of the First Hospital of China Medical University (FSFH1208). The funders had no role in study design,data collection and analysis, decision to publish, or preparation of the manuscript.