Prognostic significance of sirtuin 2 protein nuclear localization in glioma: an immunohistochemical study

The sirtuin 2 (SIRT2) protein is a member of the sirtuin family and homologous to Sir2 (silent information regulator 2) of Saccharomyces cerevisiae. To assess the pathobiological significance of SIRT2 protein expression and/or subcellular localization in human glioma, we examined SIRT2 protein expression in human gliomas using a polyclonal anti-SIRT2 antibody and immunohistochemistry. In this study, samples from 23 patients with glioblastoma (GB, grade IV), 8 patients with diffuse astrocytoma (DA, grade II) and 5 healthy individuals were examined. We established a SIRT2 labeling index (SIRT2-LI) that represents the percentage of cells with SIRT2 localized to the nucleus. The mean SIRT2-LI was 65.8±18.6 in GB samples, 41.2±22.8 in DA samples, and 28.6±12.3 in normal control samples. The SIRT2-LI of GB samples was significantly higher than that of normal control samples (P<0.01, Mann-Whitney's U-test) and that of DA samples (P<0.05). Moreover, the SIRT2-LI was positively correlated with malignant progression. Specifically, samples from patients with GB were divided into two groups, low SIRT2-LI (<60%) and high SIRT2-LI (≥60%), and the patients with low SIRT2-LI samples survived significantly longer than patients with high SIRT2-LI samples (P<0.05, Kaplan-Meier method and log-rank test). In conclusion, SIRT2-LI was indicative of glioma malignancy, and it may be predictive of GB patient survival.