SIRT5 downregulation is associated with poor prognosis in glioblastoma

Article type: Research Article

Authors: Chen, Xi^{a; b} | Xu, Zhijie^{c; *} | Zeng, Shuangshuang^{a; b} | Wang, Xiang^{a; b} | Liu, Wanli^{a; b} | Qian, Long^{a; b} | Wei, Jie^{a; b} | Yang, Xue^{a; b} | Shen, Qiuying^{a; b} | Gong, Zhicheng^{a; b} | Yan, Yuanliang^{a; b; *}

Affiliations: [a] Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China | [b] Institute for Rational and Safe Medication Practices, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China | [c] Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China

Correspondence: [*] Corresponding author: Zhijie Xu, Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China. E-mail: [email protected]; Yuanliang Yan, Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China. E-mail: [email protected].

Abstract: OBJECTIVE: Sirtuins (SIRT) are NAD+-dependent protein deacetylases that are involved in the regulation of cancer-associated pathways. However, the biological role of these deacetylases remains elusive in glioblastoma (GBM). Here, we evaluated the effects of 7 sirtuins regarding their occurrence and prognostic value for GBM. METHODS: In this research, the effects of SIRT5 on the occurrence and prognosis of GBM were evaluated using integrative bioinformatics analyses. RESULTS: Based on comprehensive analyses of data obtained from web-based bioinformatics platforms, the data demonstrate that only SIRT5 expression is statistically decreased in GBM tissues. The clinical relevance analysis shows that downregulation of SIRT5 is significantly correlated with a shorter survival time. Moreover, the expression levels of SIRT5 were confirmed to be negatively associated with DNA methylation status. In addition, a protein-protein interaction network was constructed to determine the relationship of genes coexpressed with SIRT5. Functional enrichment analysis revealed that SIRT5 was potentially involved in epithelial-mesenchymal transition and in regulating cell communications. CONCLUSIONS: Collectively, our results indicate that SIRT5 acts as a potential suppresser during tumorigenesis, and suggest that SIRT5 may be a promising prognostic biomarker of GBM.

Keywords: Glioblastoma, SIRT5, prognosis, overall survival, DNA methylation

DOI: 10.3233/CBM-182197

Journal: Cancer Biomarkers, vol. 24, no. 4, pp. 449-459, 2019