Cancer Associated Fibroblasts in Stage I-IIIA NSCLC: Prognostic Impact and Their Correlations with Tumor Molecular Markers

• Published in: PloS one 2015-08, Vol.10 (8), p.e0134965-e0134965
• Main Authors: Kilvaer, Thomas K, Khanehkenari, Mehrdad Rakaee, Hellevik, Turid, Al-Saad, Samer, Paulsen, Erna-Elise, Bremnes, Roy M, Busund, Lill-Tove, Donnem, Tom, Martinez, Inigo Z
• Format: Article
• Language: English
• Subjects: Actin; Actins - metabolism; Aged; Antigens; Biology; Biomarkers, Tumor - metabolism; Cancer; Cancer patients; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Care and treatment; Chemotherapy; Clinical medical disciplines: 750; Clinical medicine; Cohort Studies; Correlation; Correlation analysis; Development and progression; Disease-Free Survival; Female; Fibroblasts; Fibroblasts - metabolism; Fibroblasts - pathology; Health aspects; Hospitals; Humans; Immunohistochemistry; Immunotherapy; Klinisk medisinske fag: 750; Lung cancer; Lung diseases; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Male; Markers; Medical disciplines: 700; Medical prognosis; Medicine; Medisinske Fag: 700; Metastases; Middle Aged; Molecular chains; Muscle proteins; Muscles; Neoplasm Staging; Non-small cell lung cancer; Non-small cell lung carcinoma; Observer Variation; Oncology; Oncology: 762; Onkologi: 762; Pathology; Patient outcomes; Patients; Physiological aspects; Prognosis; Protein Tyrosine Phosphatase, Non-Receptor Type 13 - metabolism; Proteins; Risk factors; Smooth muscle; Squamous cell carcinoma; Statistics, Nonparametric; Stromal Cells - metabolism; Stromal Cells - pathology; Studies; Survival; Tissue Array Analysis; Tumors; VDP; Wound healing
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0134965

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. 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. 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. 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.