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

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 u...

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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
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creator Kilvaer, Thomas K
Khanehkenari, Mehrdad Rakaee
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Donnem, Tom
Martinez, Inigo Z
description 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.
doi_str_mv 10.1371/journal.pone.0134965
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Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agriculture Science Database</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>Advanced Technologies &amp; Aerospace Database</collection><collection>ProQuest Advanced Technologies &amp; Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials science collection</collection><collection>Publicly Available Content (ProQuest)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>NORA - Norwegian Open Research Archives</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kilvaer, Thomas K</au><au>Khanehkenari, Mehrdad Rakaee</au><au>Hellevik, Turid</au><au>Al-Saad, Samer</au><au>Paulsen, Erna-Elise</au><au>Bremnes, Roy M</au><au>Busund, Lill-Tove</au><au>Donnem, Tom</au><au>Martinez, Inigo Z</au><au>Gullberg, Donald</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cancer Associated Fibroblasts in Stage I-IIIA NSCLC: Prognostic Impact and Their Correlations with Tumor Molecular Markers</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2015-08-07</date><risdate>2015</risdate><volume>10</volume><issue>8</issue><spage>e0134965</spage><epage>e0134965</epage><pages>e0134965-e0134965</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>26252379</pmid><doi>10.1371/journal.pone.0134965</doi><oa>free_for_read</oa></addata></record>
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identifier ISSN: 1932-6203
ispartof PloS one, 2015-08, Vol.10 (8), p.e0134965-e0134965
issn 1932-6203
1932-6203
language eng
recordid cdi_plos_journals_1702213103
source PubMed (Medline); NORA - Norwegian Open Research Archives; Publicly Available Content (ProQuest)
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
title Cancer Associated Fibroblasts in Stage I-IIIA NSCLC: Prognostic Impact and Their Correlations with Tumor Molecular Markers
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