Clinical implications of fibroblast activation protein-α in non-small cell lung cancer after curative resection: a new predictor for prognosis

J Cancer Res Clin Oncol. 2013 Sep;139(9):1523-8. doi: 10.1007/s00432-013-1471-8. Epub 2013 Jul 9.


Background: Fibroblast activation protein-α (FAP-α), which is a serine protease specially expressed on the surface of the cancer stromal cells, plays an important role in the progression and prognosis in diverse malignancies. However, the role of FAP-α in non-small cell lung cancer (NSCLC) is still unknown.

Materials and methods: We enrolled 59 NSCLC patients who received complete resection. Sections of paraffin-embedded primary NSCLC specimens of all the patients were stained with antibody directed against FAP-α. Overall, percentage (Grade 0-3) and intensity (0-3+) of stromal FAP-α staining of the tumor were assessed.

Results: FAP-α was detected in >76 % of the specimens examined, and its high expression seemed to be correlated with poor tumor differentiation (P = 0.06). Furthermore, both increased FAP-α staining percentage and intensity were associated with worse overall survival of the patients (percentage, P = 0.0087; intensity, P = 0.05). Higher FAP-α staining percentage was observed in those patients with increased peripheral neutrophil and lymphocyte count ratio (P = 0.034).

Conclusions: FAP-α is highly expressed in cancer stroma and also a predictor of poor survival of NSCLC patients. Elevated FAP-α expression may be associated with inflammation and suppressed lymphocyte-dependent immune response, which then result in the tumor progression. Therefore, FAP-α plays an important role in the progression of NSCLC, and its high expression is a predictor of poor survival. Targeting FAP-α may be a novel strategy for NSCLC therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / mortality
  • Adenocarcinoma / surgery
  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / surgery
  • Carcinoma, Squamous Cell / metabolism*
  • Carcinoma, Squamous Cell / mortality
  • Carcinoma, Squamous Cell / surgery
  • Disease Progression
  • Endopeptidases
  • Female
  • Follow-Up Studies
  • Gelatinases / metabolism*
  • Humans
  • Immunoenzyme Techniques
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / surgery
  • Lymphatic Metastasis
  • Lymphocytes / immunology
  • Lymphocytes / metabolism
  • Lymphocytes / pathology
  • Male
  • Membrane Proteins / metabolism*
  • Middle Aged
  • Neoplasm Staging
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Neutrophils / pathology
  • Prognosis
  • Serine Endopeptidases / metabolism*
  • Survival Rate


  • Biomarkers, Tumor
  • Membrane Proteins
  • Endopeptidases
  • Serine Endopeptidases
  • fibroblast activation protein alpha
  • Gelatinases