Overexpression of fibroblast activation protein and its clinical implications in patients with osteosarcoma

J Surg Oncol. 2013 Sep;108(3):157-62. doi: 10.1002/jso.23368. Epub 2013 Jun 28.

Abstract

Background and objectives: Fibroblast activation protein (FAP) expression has been detected in fibroblastic component of osteosarcomas. The aim of this study was to analyze the correlation of FAP expression with the clinicopathological features of osteosarcoma.

Methods: FAP mRNA and protein expression levels in human osteosarcoma tissues were, respectively detected by RT-PCR, Western blot, and immunohistochemistry assays.

Results: FAP mRNA and protein expression were both higher in osteosarcoma than in corresponding noncancerous bone tissues (both P < 0.001). In addition, the immunohistochemistry assay found that all patients showed positive FAP expression. Higher FAP expression was significantly correlated with advanced clinical stage (P = 0.006), high histological grade (P = 0.02), positive metastatic status (P = 0.01), shorter overall (P < 0.001), and disease-free (P < 0.001) survival in osteosarcoma patients. Furthermore, Cox multivariate analysis showed that FAP overexpression was an independent prognostic factor for predicting both overall and disease-free survival of osteosarcoma patients.

Conclusion: Expression of FAP in osteosarcoma could be adopted as a candidate biomarker for the diagnosis of clinical stage, histological grade and metastasis, and for assessing prognosis, indicating for the first time that FAP may play an important role in tumor development and progression in osteosarcoma. FAP might be considered as a novel therapeutic target against this cancer.

Keywords: disease-free survival; fibroblast activation protein; osteosarcoma; overall survival; prognosis.

MeSH terms

  • Adult
  • Aged
  • Bone Neoplasms / chemistry
  • Bone Neoplasms / etiology
  • Bone Neoplasms / mortality
  • Bone Neoplasms / pathology*
  • Endopeptidases
  • Female
  • Gelatinases / analysis
  • Gelatinases / genetics
  • Gelatinases / physiology*
  • Humans
  • Immunohistochemistry
  • Male
  • Membrane Proteins / analysis
  • Membrane Proteins / genetics
  • Membrane Proteins / physiology*
  • Middle Aged
  • Osteosarcoma / chemistry
  • Osteosarcoma / etiology
  • Osteosarcoma / mortality
  • Osteosarcoma / pathology*
  • Prognosis
  • Proportional Hazards Models
  • RNA, Messenger / analysis
  • Serine Endopeptidases / analysis
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / physiology*

Substances

  • Membrane Proteins
  • RNA, Messenger
  • Endopeptidases
  • Serine Endopeptidases
  • fibroblast activation protein alpha
  • Gelatinases