Rab27a Was Identified as a Prognostic Biomaker by mRNA Profiling, Correlated with Malignant Progression and Subtype Preference in Gliomas

PURPOSE Rab27a belongs to the Rab small GTPase superfamily. The protein is membrane-bound and may be involved in protein transport and small GTPase-mediated signal transduction. Mutations in this gene are associated with Griscelli syndrome type 2. However, the prognostic and molecular features of gliomas with Rab27a expression are still unclear. EXPERIMENTAL DESIGN We used a whole-genome mRNA expression microarray dataset of 220 glioma samples from the Chinese Glioma Genome Atlas (CGGA) database (http://www.cgga.org.cn) as a discovery set. In this set, 220 gliomas, consisting of 97 WHO Grade II gliomas, 34 WHO Grade III gliomas, and 89 WHO Grade IV gliomas, were analyzed using the Kaplan-Meier method. To validate the protein expression of Rab27a, we assayed another 162 glioma samples by immunohistochemistry. Three additional datasets were obtained as validation sets. Gene ontology (GO) analysis and gene set variation analysis (GSVA) were used for the functional annotation of Rab27a in 89 WHO Grade IV gliomas. RESULTS Rab27a was significantly associated with grade progression and high mortality in all grades of glioma in the discovery set. Rab27a also showed a mesenchymal subtype, G3 subtype and isocitrate dehydrogenase 1 (IDH1) wild-type preference and association with migration. The 3 validation datasets revealed similar findings. Rab27a was more highly expressed in gliomas than in normal brain tissues, and its expression increased with glioma grade progression. CONCLUSIONS Rab27a expression was significantly associated with grade progression and worse prognosis in all grades of gliomas, suggesting Rab27a as a novel biomarker with potentially important therapeutic implications.