title: Cancer Associated Fibroblasts in Stage I-IIIA NSCLC: Prognostic Impact and Their Correlations with Tumor Molecular Markers.
abstract: BACKGROUND
  Cancer Associated Fibroblasts (CAFs) are thought to regulate tumor growth and metastasis. Fibroblast Activating Protein 1 (FAP-1) is a marker for fibroblast activation and by many recognized as the main marker of CAFs. Alpha Smooth Muscle Actin (α-SMA) is a general myofibroblast marker, and can be used to identify CAFs. This study investigates the prognostic impact of FAP-1 and α-SMA in non-small cell lung cancer (NSCLC) patients and correlates their expression to 105 proteins investigated in the same cohort.
  
  
  METHODS
  Tumor specimens from 536 NSCLC patients were obtained and tissue micro-arrays were constructed. Immunohistochemistry was used to evaluate the expression of FAP-1 and α-SMA and explore their impact on survival and association with other tumor molecular markers in NSCLC patients.
  
  
  RESULTS
  High expression of FAP-1, but not α-SMA, in squamous cell carcinoma (SCC, P = 0.043, HR = 0.63 95% CI 0.40-0.99) was significantly associated with increased disease-specific survival. FAP-1 and α-SMA were not significantly correlated to each other. Analyses of FAP-1 and α-SMA associated with other tumor-related proteins revealed histotype-specific correlation patterns.
  
  
  CONCLUSIONS
  The presence of FAP-1 expressing CAFs is an indicator of positive outcome for NSCLC-SCC patients. In addition, correlation analyses suggest FAP-1 and α-SMA to label different subsets of fibroblasts and their associations with other tumor-related proteins diverge according to histological subtype.
authors.affiliation: Department of Oncology, University Hospital of North Norway, Tromso, Norway; Institute of Clinical Medicine, UiT The Arctic University of Norway, Tromso, Norway.
authors.forename: Thomas K
authors.initials: TK
authors.lastname: Kilvaer
authors.affiliation: Institute of Medical Biology, UiT The Arctic University of Norway, Tromso, Norway.
authors.forename: Mehrdad Rakaee
authors.initials: MR
authors.lastname: Khanehkenari
authors.affiliation: Department of Oncology, University Hospital of North Norway, Tromso, Norway.
authors.forename: Turid
authors.initials: T
authors.lastname: Hellevik
authors.affiliation: Institute of Medical Biology, UiT The Arctic University of Norway, Tromso, Norway; Department of Clinical Pathology, University Hospital of North Norway, Tromso, Norway.
authors.forename: Samer
authors.initials: S
authors.lastname: Al-Saad
authors.affiliation: Department of Oncology, University Hospital of North Norway, Tromso, Norway; Institute of Clinical Medicine, UiT The Arctic University of Norway, Tromso, Norway.
authors.forename: Erna-Elise
authors.initials: EE
authors.lastname: Paulsen
authors.affiliation: Department of Oncology, University Hospital of North Norway, Tromso, Norway; Institute of Clinical Medicine, UiT The Arctic University of Norway, Tromso, Norway.
authors.forename: Roy M
authors.initials: RM
authors.lastname: Bremnes
authors.affiliation: Institute of Medical Biology, UiT The Arctic University of Norway, Tromso, Norway; Department of Clinical Pathology, University Hospital of North Norway, Tromso, Norway.
authors.forename: Lill-Tove
authors.initials: LT
authors.lastname: Busund
authors.affiliation: Department of Oncology, University Hospital of North Norway, Tromso, Norway; Institute of Clinical Medicine, UiT The Arctic University of Norway, Tromso, Norway.
authors.forename: Tom
authors.initials: T
authors.lastname: Donnem
authors.affiliation: Institute of Medical Biology, UiT The Arctic University of Norway, Tromso, Norway.
authors.forename: Inigo Z
authors.initials: IZ
authors.lastname: Martinez
mesh_terms: D000199:Actins / Q000378:metabolism; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism / Q000473:pathology*; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D015588:Observer Variation; D011379:Prognosis; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13 / Q000378:metabolism; D018709:Statistics, Nonparametric; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D046888:Tissue Array Analysis
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D014408:Biomarkers, Tumor; C516742:PTPN13 protein, human; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13