Decreased concentrations of intracellular signaling proteins in colon cancer patients with BRAF mutations

Autor:	Caroline Brenner Thomsen, Ivan Brandslund, Dorte Aa. Olsen, Jonna Skov Madsen, Rikke F. Andersen, Anders Jakobsen
Jazyk:	angličtina
Rok vydání:	2020
Předmět:	0301 basic medicine MAPK/ERK pathway Male Proto-Oncogene Proteins B-raf Colorectal cancer Cyclin D lcsh:Medicine Gene mutation medicine.disease_cause Biochemistry Disease-Free Survival Article 03 medical and health sciences 0302 clinical medicine medicine Humans Phosphorylation Extracellular Signal-Regulated MAP Kinases lcsh:Science Protein kinase B Aged Cancer Aged 80 and over Mutation Multidisciplinary biology business.industry lcsh:R Middle Aged medicine.disease digestive system diseases 030104 developmental biology 030220 oncology & carcinogenesis Colonic Neoplasms biology.protein Cancer research Female lcsh:Q KRAS business Proto-Oncogene Proteins c-akt Intracellular
Zdroj:	Scientific Reports, Vol 10, Iss 1, Pp 1-9 (2020) Scientific Reports Olsen, D A, Thomsen, C E B, Andersen, R F, Madsen, J S, Jakobsen, A & Brandslund, I 2020, ' Decreased concentrations of intracellular signaling proteins in colon cancer patients with BRAF mutations ', Scientific Reports, vol. 10, 20113 . https://doi.org/10.1038/s41598-020-77109-8
ISSN:	2045-2322
DOI:	10.1038/s41598-020-77109-8
Popis:	The activation of intracellular signaling pathways plays a critical role in cancer pathogenesis. The current study aims to quantify intracellular signaling proteins in localized colon cancer tissue to investigate the prognostic value of these biomarkers and elucidate their possible relations to mutation status. Colon cancer tissue and autologous reference tissue were collected from 176 patients who underwent colon cancer surgery. Assays were developed to quantify ERK, AKT and cyclin d using single-molecule array technology. KRAS/BRAF/PIK3CA mutation status was determined using droplet digital PCR. Patients with BRAF mutations had decreased concentrations of ERK (p = 0.0003), AKT (p = 0.0001) and cyclin d (p = 0.003), while no significant differences were found between patients with KRAS mutations and wild-type patients. None of the investigated proteins were associated with disease-free survival or overall survival when all patients were included. However, when patients were stratified according to mutation status, significant correlations with overall survival were seen for patients with BRAF mutations and AKT (p = 0.002) or ERK (p = 0.03) and for KRAS mutations and cyclin d (p = 0.01). Conclusions: A strong correlation exists between intracellular signaling protein concentrations and mutational BRAF status. Overall survival in colon cancer patients depends on both gene mutation status and signaling protein concentrations.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::49b99b9fe35e5841e55ace463d0d950b http://link.springer.com/article/10.1038/s41598-020-77109-8 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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