SIRT2 is an unfavorable prognostic biomarker in patients with acute myeloid leukemia.

Ailing Deng,Qiaoyang Ning,Lei Zhou,Yaojie Liang

doi:10.1038/srep27694

Abstract

SIRT2 is a member of the NAD+ dependent deacetylases. In this study, the associations between SIRT2 expression and molecular and clinical characteristics of patients with acute myeloid leukemia (AML) were evaluated by data from The Cancer Genome Atlas. SIRT2 was overexpressed in the intermediate- and poor-risk groups of patients, compared to the favorable-risk group of patients (P = 0.002 and 0.004, respectively). High SIRT2 expression was associated with significantly shorter overall survival (OS; P = 0.0005) and event-free survival (EFS; P = 0.0002) than low SIRT2 expressio in a cohort of 167 patients with AML. Multivariate analyses revealed that high SIRT2 expression was associated with shorter OS (P = 0.031) and EFS (P = 0.020). Gene-expression profiling showed 259 differential expressed genes including CD4, CD14 and IL10. Gene sets like MAPK signaling pathway, VEGF signaling pathway and acute myeloid leukemia were upregulated in SIRT2high patients. We also found different methylation patterns in these two groups. OS and EFS of SIRT2high patients who did not undergo transplantation were significantly shorter than those of SIRT2low patients (P = 0.0120 and P = 0.0107, respectively). Taken together, these findings suggest that high SIRT2 expression is a novel and unfavorable prognostic biomarker for AML risk-stratification.

Highlights

For the first time, we report the relationship between SIRT2 expression and prognosis of patients with AML, and found that high SIRT2 expression was associated with a poor prognosis in these patients
How did SIRT2 become associated with prognosis of AML patients? Previous studies revealed that SIRT2 regulates acetylation status and oncogenic activity of mutant KRAS
Inhibiting SIRT2 has a dramatic effect on the growth properties of cancer cells expressing KRAS activation mutants[21]

Summary

Introduction

The number of SIRT2high and SIRT2low patients was significantly different in the NCCN-favorable group (P = 0.012). Median OS and EFS of the SIRT2high group (7.7 and 25.8 months and 5.25 and 12 months, respectively) were significantly shorter than those of SIRT2low patients (P = 0.0005; P = 0.0002, respectively; Fig. 2), according to Gehan–Breslow–Wilcoxon test, which were revalidated by the log-rank test. High SIRT2 expression in poor-risk patients was associated with shorter EFS and OS (Fig. 3A,B).

Results

Conclusion