High Expression of FLOT1 Is Associated with Progression and Poor Prognosis in Hepatocellular Carcinoma

PLoS One. 2013 Jun 26;8(6):e64709. doi: 10.1371/journal.pone.0064709. Print 2013.

Abstract

Background: The flotillin family member flotillin-1 (FLOT1) encodes a caveolae-associated, integral membrane protein that belongs to lipid raft family and involves in vesicular trafficking and signal transduction. However, the role of FLOT1 in development and progression of cancer remains largely unknown. The present study was aimed to investigate the clinical and prognostic significance of FLOT1 in hepatocellular carcinoma (HCC).

Methods: Real-time PCR and western blot analyses were applied to examine FLOT1 expression in fourteen HCC cell lines and one normal hepatic cell line, ten pairs of primary HCC and matched adjacent noncancerous liver tissues from the same patient. Immunohistochemistry (IHC) was performed to examine FLOT1 protein expression in paraffin-embedded tissues from 196 HCC patients. Statistical analyses were applied to evaluate the diagnostic value and associations of FLOT1 expression with clinical parameters.

Results: FLOT1 expression was evidently up-regulated in HCC tissues compared with that in the matched adjacent noncancerous liver tissues. In the 196 cases of tested HCC samples, FLOT1 protein level was positively correlated with Tumor size (P = 0.025), clinical stage (P<0.002), CLIP stage (P<0.001), vascular invasion (P<0.001), relapse (P<0.001), and serum AFP levels (P = 0.025). Patients with higher FLOT1 expression had shorter overall survival time, whereas those with lower FLOT1 expression had longer survival time.

Conclusions: Our study demonstrated FLOT1 is associated with aggressive characteristics of HCC, and suggested the possibility of its use as a prognostic marker in patients with HCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Hepatocellular / diagnosis*
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Disease Progression*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Liver Neoplasms / diagnosis*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Male
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism*
  • Middle Aged
  • Prognosis
  • Up-Regulation
  • Young Adult

Substances

  • Membrane Proteins
  • flotillins

Grants and funding

This study was supported by: the Natural Science Foundation of China (No. 30901791, 81172055), National Program on Key Basic Research Project (973 Program, No. 2012CB519003), and Guangdong Provincial Natural Science Foundation of China (No. S2012010009643). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.