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SIRT3 & SIRT7: Potential Novel Biomarkers for Determining Outcome in Pancreatic Cancer Patients.

McGlynn LM, McCluney S, Jamieson NB, Thomson J, MacDonald AI, Oien K, Dickson EJ, Carter CR, McKay CJ, Shiels PG - PLoS ONE (2015)

Bottom Line: Statistical analyses determined if SIRT1-7 protein expression was associated with clinical parameters or outcome.Two sirtuin family members demonstrated significant associations with clinico-pathological parameters and patient outcome.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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom.

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.

No MeSH data available.


Related in: MedlinePlus

SIRT7 may act as a prognostic factor for patients with pancreatic cancer.Survival analysis of the entire cohort did not reveal any significant differences in (a) disease-free survival or (b) disease-specific survival time between patients whose tumours had low or high SIRT7 nuclear expression. However, it was apparent from the survival plots that there was a division of the low/high SIRT7 expression lines at approximately 12–14 months. Analysis was therefore performed on the subset of patients that survived longer than 12 months (n = 44). Patients with low SIRT7 nuclear expression exhibited (c) a shorter disease-free survival time (p = 0.028, 20.1 vs 38 months) and (d) a decrease in disease-specific time (p = 0.026, 26.9 vs 43.1 months) than patients whose tumour expressed high SIRT7 levels.
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pone.0131344.g005: SIRT7 may act as a prognostic factor for patients with pancreatic cancer.Survival analysis of the entire cohort did not reveal any significant differences in (a) disease-free survival or (b) disease-specific survival time between patients whose tumours had low or high SIRT7 nuclear expression. However, it was apparent from the survival plots that there was a division of the low/high SIRT7 expression lines at approximately 12–14 months. Analysis was therefore performed on the subset of patients that survived longer than 12 months (n = 44). Patients with low SIRT7 nuclear expression exhibited (c) a shorter disease-free survival time (p = 0.028, 20.1 vs 38 months) and (d) a decrease in disease-specific time (p = 0.026, 26.9 vs 43.1 months) than patients whose tumour expressed high SIRT7 levels.

Mentions: Survival analysis did not reveal any significant differences in disease-free or disease-specific survival time between patients whose tumours had low or high SIRT7 nuclear expression. However, it was apparent from the survival plots that there was a division of the low/high SIRT7 expression lines at approximately 12–14 months (Fig 5A and 5B). Analysis was therefore performed on the subset of patients that survived longer than 12 months (n = 44). Patients with low SIRT7 nuclear expression exhibited a shorter disease-free survival time (p = 0.028, mean disease-free time 20.1 vs 38 months, HR = 2.05 (1.07–3.92) p = 0.031, Fig 5C). Multivariate cox–regression analysis revealed that nuclear SIRT7 expression (p = 0.023) and lymph node status (p = 0.004) were independent of tumour differentiation, stage and grade, in influencing disease-free survival.


SIRT3 & SIRT7: Potential Novel Biomarkers for Determining Outcome in Pancreatic Cancer Patients.

McGlynn LM, McCluney S, Jamieson NB, Thomson J, MacDonald AI, Oien K, Dickson EJ, Carter CR, McKay CJ, Shiels PG - PLoS ONE (2015)

SIRT7 may act as a prognostic factor for patients with pancreatic cancer.Survival analysis of the entire cohort did not reveal any significant differences in (a) disease-free survival or (b) disease-specific survival time between patients whose tumours had low or high SIRT7 nuclear expression. However, it was apparent from the survival plots that there was a division of the low/high SIRT7 expression lines at approximately 12–14 months. Analysis was therefore performed on the subset of patients that survived longer than 12 months (n = 44). Patients with low SIRT7 nuclear expression exhibited (c) a shorter disease-free survival time (p = 0.028, 20.1 vs 38 months) and (d) a decrease in disease-specific time (p = 0.026, 26.9 vs 43.1 months) than patients whose tumour expressed high SIRT7 levels.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4487247&req=5

pone.0131344.g005: SIRT7 may act as a prognostic factor for patients with pancreatic cancer.Survival analysis of the entire cohort did not reveal any significant differences in (a) disease-free survival or (b) disease-specific survival time between patients whose tumours had low or high SIRT7 nuclear expression. However, it was apparent from the survival plots that there was a division of the low/high SIRT7 expression lines at approximately 12–14 months. Analysis was therefore performed on the subset of patients that survived longer than 12 months (n = 44). Patients with low SIRT7 nuclear expression exhibited (c) a shorter disease-free survival time (p = 0.028, 20.1 vs 38 months) and (d) a decrease in disease-specific time (p = 0.026, 26.9 vs 43.1 months) than patients whose tumour expressed high SIRT7 levels.
Mentions: Survival analysis did not reveal any significant differences in disease-free or disease-specific survival time between patients whose tumours had low or high SIRT7 nuclear expression. However, it was apparent from the survival plots that there was a division of the low/high SIRT7 expression lines at approximately 12–14 months (Fig 5A and 5B). Analysis was therefore performed on the subset of patients that survived longer than 12 months (n = 44). Patients with low SIRT7 nuclear expression exhibited a shorter disease-free survival time (p = 0.028, mean disease-free time 20.1 vs 38 months, HR = 2.05 (1.07–3.92) p = 0.031, Fig 5C). Multivariate cox–regression analysis revealed that nuclear SIRT7 expression (p = 0.023) and lymph node status (p = 0.004) were independent of tumour differentiation, stage and grade, in influencing disease-free survival.

Bottom Line: Statistical analyses determined if SIRT1-7 protein expression was associated with clinical parameters or outcome.Two sirtuin family members demonstrated significant associations with clinico-pathological parameters and patient outcome.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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Cancer Sciences, University of Glasgow, Glasgow, United Kingdom.

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.

No MeSH data available.


Related in: MedlinePlus