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Stromal FAP is an i...
Stromal FAP is an independent poor prognosis marker in non-small cell lung adenocarcinoma and associated with p53 mutation
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- Moreno-Ruiz, Pablo (author)
- Karolinska Inst, Canc Ctr Karolinska, Dept Oncol Pathol, Stockholm, Sweden
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- Corvigno, Sara (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi,Science for Life Laboratory, SciLifeLab,Karolinska Inst, Canc Ctr Karolinska, Dept Oncol Pathol, Stockholm, Sweden
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- te Grootenhuis, Nienke C. (author)
- Univ Groningen, Univ Med Ctr Groningen, Dept Obstet & Gynecol, Groningen, Netherlands
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- La Fleur, Linnéa (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Klinisk och experimentell patologi
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- Backman, Max (author)
- Uppsala universitet,Klinisk och experimentell patologi,Science for Life Laboratory, SciLifeLab,Patrick Micke
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- Strell, Carina (author)
- Karolinska Inst, Canc Ctr Karolinska, Dept Oncol Pathol, Stockholm, Sweden
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- Mezheyeuski, Artur (author)
- Uppsala universitet,Experimentell och klinisk onkologi,Science for Life Laboratory, SciLifeLab,Karolinska Inst, Canc Ctr Karolinska, Dept Oncol Pathol, Stockholm, Sweden
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- Hoelzlwimmer, Gabriele (author)
- Roche Innovat Ctr Munich Penzberg, Penzberg, Germany
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- Klein, Christian (author)
- Roche Innovat Ctr Zurich, Schlieren, Switzerland
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- Botling, Johan (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Klinisk och experimentell patologi,Johan Botling
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- Micke, Patrick (author)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Klinisk och experimentell patologi,Patrick Micke
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- Östman, Arne (author)
- Karolinska Institutet
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(creator_code:org_t)
- Elsevier, 2021
- 2021
- English.
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In: Lung Cancer. - : Elsevier. - 0169-5002 .- 1872-8332. ; 155, s. 10-19
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Abstract
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- ObjectivesFibroblasts regulate tumor growth and immune surveillance. Here, we study FAP, PDGFβR and α-SMA fibroblast markers in a well-annotated clinical cohort of non–small-cell lung cancer (NSCLC) for analyses of associations with immune cell infiltration, mutation status and survival.Materials and MethodsA well-annotated NSCLC cohort was subjected to IHC analyses of stromal expression of FAP, PDGFβR and α-SMA and of stromal CD8 density. Fibroblast markers-related measurements were analyzed with regard to potential associations with CD8 density, cancer genetic driver mutations, survival and PD-L1 expression in the whole NSCLC cohort and in subsets of patients.ResultsHigh stromal FAP expression was identified as an independent poor prognostic marker in the whole study population (HR 1.481; 95 % CI, 1.012–2.167, p = 0.023) and in the histological subset of adenocarcinoma (HR 1.720; 95 % CI, 1.126–2.627, p = 0.012). Among patients with adenocarcinoma, a particularly strong association of FAP with poor survival was detected in patients with low stromal CD8 infiltration, and in other subpopulations identified by specific clinical characteristics; elderly patients, females, non-smokers and patients with normal ECOG performance status. α-SMA expression was negatively associated with CD8 infiltration in non-smokers, but none of the fibroblast markers expression was associated with CD8 density in the whole study population. Significant associations were detected between presence of p53 mutations and high α-SMA (p = 0.003) and FAP expression (p < 0.001).ConclusionThe study identifies FAP intensity as a candidate independent NSCLC prognostic biomarker. The study also suggests continued analyses of the relationships between genetic driver mutations and the composition of tumor stroma, as well as continued probing of marker-defined fibroblasts as NSCLC subset-specific modifiers of immune surveillance and outcome.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Klinisk laboratoriemedicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Clinical Laboratory Medicine (hsv//eng)
Keyword
- FAP
- Fibroblast
- Stroma
- PDGFβR
- α-SMA
- Biomarkers
- CD8
- Non-small-cell lung cancer
- Pathology
- Patologi
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Moreno-Ruiz, Pab ...
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Corvigno, Sara
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te Grootenhuis, ...
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La Fleur, Linnéa
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Backman, Max
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Strell, Carina
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show more...
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Mezheyeuski, Art ...
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Hoelzlwimmer, Ga ...
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Klein, Christian
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Botling, Johan
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Micke, Patrick
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Östman, Arne
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Clinical Laborat ...
- Articles in the publication
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Lung Cancer
- By the university
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Uppsala University
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Karolinska Institutet