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Protein Kinase C Isozymes Associated With Relapse Free Survival in Non-Small Cell Lung Cancer Patients.


ABSTRACT:

Introduction

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.

Methods

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.

Results

Spearman's rank correlation analysis identified 46 proteins with significant association to RFS (p<0.05). High expression of protein kinase C (PKC)-? and the phosporylated state of PKC-?, PKC-?, and PKC-?, 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.

Conclusion

This study identified different proteins associated with RFS depending on molecular subtype, smoking- and mutational-status, with PKC-?, PKC-?, and PKC-? showing the strongest correlation.

SUBMITTER: Halvorsen AR 

PROVIDER: S-EPMC7725872 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Protein Kinase C Isozymes Associated With Relapse Free Survival in Non-Small Cell Lung Cancer Patients.

Halvorsen Ann Rita AR   Haugen Mads Haugland MH   Öjlert Åsa Kristina ÅK   Lund-Iversen Marius M   Jørgensen Lars L   Solberg Steinar S   Mælandsmo Gunhild M GM   Brustugun Odd Terje OT   Helland Åslaug Å  

Frontiers in oncology 20201125


<h4>Introduction</h4>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 <i>EGFR-</i>, <i>TP53-</i>, and <i>KRAS</i>-mutations.<h4>Methods</h4>We performed profiling of 295 cancer-relevant phosphorylated and non-phosphorylated proteins, using rev  ...[more]

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