Notch3 and HEY-1 as prognostic biomarkers in pancreatic adenocarcinoma..pdf (1.13 MB)
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Notch3 and HEY-1 as prognostic biomarkers in pancreatic adenocarcinoma

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journal contribution
posted on 14.04.2016, 11:42 by C. D. Mann, C. Bastianpillai, C. P. Neal, M. M. Masood, D. J. Jones, F. Teichert, R. Singh, E. Karpova, D. P. Berry, Margaret M. Manson
In order to achieve a better outcome for pancreatic cancer patients, reliable biomarkers are required which allow for improved diagnosis. These may emanate from a more detailed molecular understanding of the aggressive nature of this disease. Having previously reported that Notch3 activation appeared to be associated with more aggressive disease, we have now examined components of this pathway (Notch1, Notch3, Notch4, HES-1, HEY-1) in more detail in resectable (n = 42) and non-resectable (n = 50) tumours compared to uninvolved pancreas. All three Notch family members were significantly elevated in tumour tissue, compared to uninvolved pancreas, with expression maintained within matched lymph node metastases. Furthermore, significantly higher nuclear expression of Notch1, -3 and -4, HES-1, and HEY-1 (all p ≤ 0.001) was noted in locally advanced and metastatic tumours compared to resectable cancers. In survival analyses, nuclear Notch3 and HEY-1 expression were significantly associated with reduced overall and disease-free survival following tumour resection with curative intent, with nuclear HEY-1 maintaining independent prognostic significance for both outcomes on multivariate analysis. These data further support a central role for Notch signalling in pancreatic cancer and suggest that nuclear expression of Notch3 and its target gene, HEY-1, merit validation in biomarker panels for diagnosis, prognosis and treatment efficacy. A peptide fragment of Notch3 was detected in plasma from patients with inoperable pancreatic cancer, but due to wide inter-individual variation, mean levels were not significantly different compared to age-matched controls.

History

Citation

PLoS One, 2012, 7 (12), e51119

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicine/Department of Cancer Studies and Molecular Medicine

Version

VoR (Version of Record)

Published in

PLoS One

Publisher

Public Library of Science

eissn

1932-6203

Acceptance date

21/10/2001

Copyright date

2012

Available date

14/04/2016

Publisher version

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0051119

Language

en