RIT1: A Novel Biomarker in Glioblastoma

Abstract

Glioblastoma is the most common type of malignant brain tumors and the most feared cancer among adults. Its high invasiveness and the lack of successful therapies are responsible for the poor prognosis among these patients. A comprehensive understanding for the early molecular mechanisms in glioblastoma would definitely enhance its diagnosis and treatment strategies. Based on in vitro and in vivo models, it was recently postulated that the deregulated expression of key genes that are known to be involved in early neurogenesis could be the instigator of brain tumorigenesis. RIT1 (Ras Like Without CAAX 1) which encodes an unusual "orphan" GTPase protein belongs to this category of critical genes involved in controlling sequential proliferation and differentiation of adult hippocampal neural progenitor cells. As such, we surveyed RIT1 expression and its potential role in glioblastoma by in-silico means. Our results revealed a significant and progressive upregulation of RIT1 expression in various publicly available datasets. RIT1 expression ranked among the top upregulated genes in glioblastoma cohorts and correlated with poor overall survival. Genetic and epigenetic analysis of RIT1 didnt reveal significant aberrations that could underlie its deregulated expression. Moreover, our results pointed on RIT1 transcriptional activity that could be significantly controlled by STAT3, one of the main players in the onset of glioblastoma. In conclusion, our results are the first proof for the role of RIT1 as an oncogene in glioblastoma paving the way for its potential use as a biomarker and therapeutic target as is the case of the other members in the RAS family.