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. 2015 Aug 7;10(8):e0134965.
doi: 10.1371/journal.pone.0134965. eCollection 2015.

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

Thomas K Kilvaer  1 , Mehrdad Rakaee Khanehkenari  2 , Turid Hellevik  3 , Samer Al-Saad  4 , Erna-Elise Paulsen  1 , Roy M Bremnes  1 , Lill-Tove Busund  4 , Tom Donnem  1 , Inigo Z Martinez  2
Affiliations

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

Thomas K Kilvaer et al. PLoS One. .

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.

Conclusion: 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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1
A) IHC analysis of TMA cores from NSCLC patients representing different stromal cell scores for expression of FAP-1 and α-SMA. I) Low stromal FAP-1; II) High stromal FAP-1; III) Low stromal α-SMA; IV) High stromal α-SMA. B) TMA control of healthy lung tissue showing strong FAP-1 positivity in normal lung macrophages, C) TMA control of healthy lung tissue showing some weak to intermediate α-SMA staining, D) Western blot for FAP-1 showing one clear 70 kDa band. Abbreviations: FAP-1, Fibroblast activating protein; α-SMA, alpha-smooth muscle actin.
Fig 2
Fig 2. Disease-specific survival curves for A) FAP-1 in the overall cohort; B) FAP-1 in SCC; C) FAP-1 in ADC; D) α-SMA in the overall cohort; E) α-SMA in SCC; F) α-SMA in ADC.
Abbreviations:SCC, squamous-cell carcinoma; ADC, adenocarcinoma; FAP-1, Fibroblast activating protein; α-SMA, alpha-smooth muscle actin.
See this image and copyright information in PMC

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