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dc.contributor.authorHalvorsen, Ann Rita
dc.contributor.authorHaugen, Mads Haugland
dc.contributor.authorØjlert, Åsa Kristina
dc.contributor.authorLund-Iversen, Marius
dc.contributor.authorJørgensen, Lars Hilmar
dc.contributor.authorSolberg, Steinar
dc.contributor.authorMælandsmo, Gunhild Mari
dc.contributor.authorBrustugun, Odd Terje
dc.contributor.authorHelland, Åslaug
dc.date.accessioned2021-02-26T08:59:32Z
dc.date.available2021-02-26T08:59:32Z
dc.date.issued2020-11-25
dc.description.abstract<i>Introduction</i>: Protein expression is deregulated in cancer, and the proteomic changes observed in lung cancer may be a consequence of mutations in essential genes. The purpose of this study was to identify protein expression associated with prognosis in lung cancers stratified by smoking status, molecular subtypes, and EGFR-, TP53-, and KRAS-mutations.<p> <p><i>Methods</i>: We performed profiling of 295 cancer-relevant phosphorylated and non-phosphorylated proteins, using reverse phase protein arrays. Biopsies from 80 patients with operable lung adenocarcinomas were analyzed for protein expression and association with relapse free survival (RFS) were studied.<p> <p><i>Results</i>: Spearman’s rank correlation analysis identified 46 proteins with significant association to RFS (p<0.05). High expression of protein kinase C (PKC)-α and the phosporylated state of PKC-α, PKC-β, and PKC-δ, showed the strongest positive correlation to RFS, especially in the wild type samples. This was confirmed in gene expression data from 172 samples. Based on protein expression, unsupervised hierarchical clustering separated the samples into four subclusters enriched with the molecular subtypes terminal respiratory unit (TRU), proximal proliferative (PP), and proximal inflammatory (PI) (p=0.0001). Subcluster 2 contained a smaller cluster (2a) enriched with samples of the subtype PP, low expression of the PKC isozymes, and associated with poor RFS (p=0.003) compared to the other samples. Low expression of the PKC isozymes in the subtype PP and a reduced relapse free survival was confirmed with The Cancer Genome Atlas (TCGA) lung adenocarcinoma (LUAD) samples.<p> <p><i>Conclusion</i>: This study identified different proteins associated with RFS depending on molecular subtype, smoking- and mutational-status, with PKC-α, PKC-β, and PKC-δ showing the strongest correlation.en_US
dc.identifier.citationHalvorsen, Haugen, Øjlert, Lund-Iversen, Jørgensen, Solberg, Mælandsmo, Brustugun, Helland. Protein kinase C isozymes associated with relapse free survival in non-small cell lung cancer patients. Frontiers in Oncology. 2020;10:590755:1-11
dc.identifier.cristinIDFRIDAID 1887140
dc.identifier.doi10.3389/fonc.2020.590755
dc.identifier.issn2234-943X
dc.identifier.urihttps://hdl.handle.net/10037/20607
dc.language.isoengen_US
dc.relation.journalFrontiers in Oncology
dc.rights.holderCopyright 2020 The Author(s)en_US
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710en_US
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710en_US
dc.titleProtein kinase C isozymes associated with relapse free survival in non-small cell lung cancer patientsen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US


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