C59

Altered Sirtuin expression in colorectal cancer

Fraser Maxwell, Conor Moran, Samer Zino, Liane McGlyn, Paul Shiels

University of Glasgow, UK

Background

Biological ageing is a complex multi-factorial process with the key determinants not yet fully elucidated. Increasing chronological age is an important risk factor for many types of cancer, hence mechanisms implicated in both processes may offer insight into what may be an important relationship. The sirtuin family of genes (SIRT 1-7) provide an intuitive link between cancer and biological ageing. These have key functions at the cellular level including regulating cellular metabolism, DNA repair, epigenetic gene silencing and cell cycle control. We have investigated the expression of SIRT 1-7 in colorectal cancer tissue.

Method

The relative expression of SIRT 1-7 was determined using quantitative real-time PCR in twenty-four matched colorectal tumour samples and adjacent non-malignant tissue. Tissue was obtained from the local Biobank and validated by a consultant pathologist. Expression levels were correlated with common clinico-pathological parameters.

Results

Expression of all but SIRT 2 was significantly reduced in tumour samples when compared with normal tissue (SIRT1 p < 0.05; SIRT3 p < 0.01; SIRT4 p < 0.01; SIRT5 p < 0.01; SIRT6 p < 0.000; SIRT7 p < 0.000). Tumour expression of SIRT5 was significantly increased in node positive patients and was associated with peritoneal involvement (chi square p < 0.05) and margin positivity (chi square p < 0.05)

Conclusion

Our results indicate that the sirtuins are differentially expressed between colorectal tumour samples and normal colonic tissue. Furthermore, tumoural expression of SIRT5 may provide a useful marker of disease severity. Further work is indicated to fully delineate the role of the sirtuins in the process of carcinogenesis.