SIRT3 & SIRT7: potential novel biomarkers for determining outcome in pancreatic cancer patients

McGlynn, L. M., McCluney, S., Jamieson, N. B. , Thomson, J., MacDonald, A. I., Oien, K. , Dickson, E. J., Carter, C. R., McKay, C. J. and Shiels, P. G. (2015) SIRT3 & SIRT7: potential novel biomarkers for determining outcome in pancreatic cancer patients. PLoS ONE, 10(6), e0131344. (doi:10.1371/journal.pone.0131344) (PMID:26121130) (PMCID:PMC4487247)

McGlynn, L. M., McCluney, S., Jamieson, N. B. , Thomson, J., MacDonald, A. I., Oien, K. , Dickson, E. J., Carter, C. R., McKay, C. J. and Shiels, P. G. (2015) SIRT3 & SIRT7: potential novel biomarkers for determining outcome in pancreatic cancer patients. PLoS ONE, 10(6), e0131344. (doi:10.1371/journal.pone.0131344) (PMID:26121130) (PMCID:PMC4487247)

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Abstract

Purpose: The sirtuin gene family has been linked with tumourigenesis, in both a tumour promoter and suppressor capacity. Information regarding the function of sirtuins in pancreatic cancer is sparse and equivocal. We undertook a novel study investigating SIRT1-7 protein expression in a cohort of pancreatic tumours. The aim of this study was to establish a protein expression profile for SIRT1-7 in pancreatic ductal adenocarcinomas (PDAC) and to determine if there were associations between SIRT1-7 expression, clinico-pathological parameters and patient outcome. Material and Methods: Immunohistochemical analysis of SIRT1-7 protein levels was undertaken in a tissue micro-array comprising 77 resected PDACs. Statistical analyses determined if SIRT1-7 protein expression was associated with clinical parameters or outcome. Results: Two sirtuin family members demonstrated significant associations with clinico-pathological parameters and patient outcome. Low level SIRT3 expression in the tumour cytoplasm correlated with more aggressive tumours, and a shorter time to relapse and death, in the absence of chemotherapeutic intervention. Low levels of nuclear SIRT7 expression were also associated with an aggressive tumour phenotype and poorer outcome, as measured by disease-free and disease-specific survival time, 12 months post-diagnosis. Conclusions: Our data suggests that SIRT3 and SIRT7 possess tumour suppressor properties in the context of pancreatic cancer. SIRT3 may also represent a novel predictive biomarker to determine which patients may or may not respond to chemotherapy. This study opens up an interesting avenue of investigation to potentially identify predictive biomarkers and novel therapeutic targets for pancreatic cancer, a disease that has seen no significant improvement in survival over the past 40 years.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Jamieson, Dr Nigel and Oien, Dr Karin and Shiels, Professor Paul and Carter, Mr Christopher and McGlynn, Dr Liane and MacDonald, Dr Alasdair
Authors: McGlynn, L. M., McCluney, S., Jamieson, N. B., Thomson, J., MacDonald, A. I., Oien, K., Dickson, E. J., Carter, C. R., McKay, C. J., and Shiels, P. G.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:PLoS ONE
Publisher:Public Library of Science
ISSN:1932-6203
ISSN (Online):1932-6203

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