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Br J Cancer. 2018 Feb 6;118(3):435-440. doi: 10.1038/bjc.2017.458. Epub 2018 Jan 23.

A core matrisome gene signature predicts cancer outcome.

Author information

1
CRUK/MRC Oxford Institute for Radiation Oncology, Old Road Campus Research Building, Roosevelt Drive, Oxford OX3 7DQ, UK.
2
Department of Hepatobiliary and Pancreatic Surgery, Oxford University Hospitals NHS Foundation Trust, Old Road, Oxford OX3 7LE, UK.
3
Nuffield Department of Surgical Sciences, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK.

Abstract

BACKGROUND:

Accumulating evidence implicates the tumour stroma as an important determinant of cancer progression but the protein constituents relevant for this effect are unknown. Here we utilised a bioinformatics approach to identify an extracellular matrix (ECM) gene signature overexpressed in multiple cancer types and strongly predictive of adverse outcome.

METHODS:

Gene expression levels in cancers were determined using Oncomine. Geneset enrichment analysis was performed using the Broad Institute desktop application. Survival analysis was performed using KM plotter. Survival data were generated from publically available genesets.

RESULTS:

We analysed ECM genes significantly upregulated across a large cohort of patients with ovarian, lung, gastric and colon cancers and defined a signature of nine commonly upregulated genes. Each of these nine genes was considerably overexpressed in all the cancers studied, and cumulatively, their expression was associated with poor prognosis across all data sets. Further, the gene signature expression was associated with enrichment of genes governing processes linked to poor prognosis, such as EMT, angiogenesis, hypoxia, and inflammation.

CONCLUSIONS:

Here we identify a nine-gene ECM signature, which strongly predicts outcome across multiple cancer types and can be used for prognostication after validation in prospective cancer cohorts.

PMID:
29360819
PMCID:
PMC5808042
DOI:
10.1038/bjc.2017.458
[Indexed for MEDLINE]
Free PMC Article

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