A combined ULBP2 and SEMA5A expression signature as a prognostic and predictive biomarker for colon cancer
Author(s)
Date
2017Source Title
Journal of Cancer
Print ISSN
1837-9664
Publisher
Ivyspring International Publisher
Volume
8
Issue
7
Pages
1113 - 1122
Language
English
Type
ArticleItem Usage Stats
238
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views
155
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Abstract
Background: Prognostic biomarkers for cancer have the power to change the course of disease if they add value beyond known prognostic factors, if they can help shape treatment protocols, and if they are reliable. The aim of this study was to identify such biomarkers for colon cancer and to understand the molecular mechanisms leading to prognostic stratifications based on these biomarkers. Methods and Findings: We used an in house R based script (SSAT) for the in silico discovery of stage-independent prognostic biomarkers using two cohorts, GSE17536 and GSE17537, that include 177 and 55 colon cancer patients, respectively. This identified 2 genes, ULBP2 and SEMA5A, which when used jointly, could distinguish patients with distinct prognosis. We validated our findings using a third cohort of 48 patients ex vivo. We find that in all cohorts, a combined ULBP2/SEMA5A classification (SU-GIB) can stratify distinct prognostic sub-groups with hazard ratios that range from 2.4 to 4.5 (p=0.01) when overall- or cancer-specific survival is used as an end-measure, independent of confounding prognostic parameters. In addition, our preliminary analyses suggest SU-GIB is comparable to Oncotype DX colon(®) in predicting recurrence in two different cohorts (HR: 1.5-2; p=0.02). SU-GIB has potential as a companion diagnostic for several drugs including the PI3K/mTOR inhibitor BEZ235, which are suitable for the treatment of patients within the bad prognosis group. We show that tumors from patients with worse prognosis have low EGFR autophosphorylation rates, but high caspase 7 activity, and show upregulation of pro-inflammatory cytokines that relate to a relatively mesenchymal phenotype. Conclusions: We describe two novel genes that can be used to prognosticate colon cancer and suggest approaches by which such tumors can be treated. We also describe molecular characteristics of tumors stratified by the SU-GIB signature.
Keywords
BiomarkerColon cancer
Prognosis
Biological marker
Caspase 7
Dactolisib
Epidermal growth factor receptor
Protein derivative
Protein sema5a
Protein ULBP2
Unclassified drug
Adult
Aged
Autophosphorylation
Cancer prognosis
Cancer recurrence
Cancer specific survival
Colon cancer
Enzyme activity
Female
Human
Human tissue
Major clinical study
Male
Microsatellite instability
Overall survival
Protein expression
Upregulation
Permalink
http://hdl.handle.net/11693/36992Published Version (Please cite this version)
https://.doi.org/10.7150/jca.17872Collections
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