RAB38 confers a poor prognosis, associated with malignant progression and subtype preference in glioma

RAB38 is a new member of the RAB small G protein family that regulates intracellular vesicle trafficking. RAB38 is expressed in melanocytes and it has been shown that a point mutation in the postulated GTP-binding domain of RAB38 is the gene responsible for human Hermansky-Pudlak syndrome. However, the prognostic and molecular features of tumors with RAB38 expression is still unclear, as well as glioma. Whole genome mRNA expression microarray data on 220 glioma samples from the Chinese Glioma Genome Atlas (CGGA) database (http://www.cgga.org.cn) was applied as discovery set. Each grade of glioma patients was analyzed by the Kaplan-Meier method. To determine the protein expression levels of RAB38, further 82 glioma tissues were stained by immunohistochemistry. Three additional datasets (TCGA, GSE16011 and Rembrandt) were obtained as validation sets. The functional annotation of RAB38 was analyzed by Gene Ontology (GO) analysis and Gene set variation analysis (GSVA) in 89 glioblastomas (GBMs). High RAB38 expression was mainly increased in high-grade gliomas, and high RAB38 expression also conferred high mortality of glioma in the CGGA cohort. RAB38 showed a mesenchymal subtype, G3 subtype and isocitrate dehydrogenase 1 (IDH1) wild-type preference. GO and GSVA analysis showed that RAB38 was significantly correlated with migration. These results were validated in other 3 datasets. The expression levels of RAB38 were significantly associated with grade progression as well as prognosis in gliomas. RAB38 is an important prognostic biomarker and potential therapeutic target in gliomas.