Abstract

   Background: Glioblastoma (GBM) represents the most malignant glioma
   among astrocytomas and is a lethal form of brain cancer. Many RAB genes
   are involved in different cancers but RAB42 (Ras-associated binding 42)
   is seldom studied in GBM. Our study aimed to explore the role of RAB42
   expression in the development and prognosis of GBM. Methods: All GBM
   patient data were obtained from The Cancer Genome Atlas (TCGA) and
   Chinese Glioma Genome Atlas (CGGA) databases. The relevance of RAB42
   expression to the clinicopathologic characteristics of GBM patients was
   analyzed. The overall survival (OS) significance was determined using
   log-rank. Significantly enriched KEGG pathways were screened using gene
   set enrichment analysis (GSEA). Results: High expression of RAB42 was
   observed in GBM specimens compared with normal samples, which was also
   verified in cell lines and tissue samples. Elevated RAB42 expression
   was correlated with higher GBM histological grade. The prognosis of GBM
   patients with high RAB42 expression was worse than those with lower
   RAB42. A total of 35 pathways, such as the P53 pathway, were
   significantly activated in highly RAB42-expressed GBM samples.
   Conclusions: High RAB42 expression is related to the development of
   GBM, and RAB42 is a probable prognostic marker for GBM.

   Keywords: glioblastoma, RAB42, The Cancer Genome Atlas, prognostic
   marker

1. Introduction

   Glioblastomas (GBM), also named WHO grade IV astrocytomas [[28]1], are
   intrinsic brain tumors [[29]2]. In addition, GBM is the most malignant
   glioma among astrocytomas and is a lethal form of brain cancer [[30]3].
   The median overall survival (OS) of GBM was just 10–20 months with
   radio- and chemotherapy in [[31]4,[32]5,[33]6]. Unlike some other
   cancers, therapies for and research into GBM are facing more challenges
   due to limited opportunities for reoperation, limited tumor locations,
   limited sample amounts, and so on [[34]7,[35]8,[36]9]. Not only that,
   there is a significantly heterogeneous inter- and intra-tumor genome in
   GBMs [[37]8], which is a problem in various kinds of cancers. However,
   based on the background of a high probability of 5-year recurrence for
   GBM [[38]10], not only do some estimates suggest that magnetic
   resonance imaging (MRI) pseudoprogression rates are close to 20%
   [[39]11] but also significant differences could be observed in the
   survival outcomes of GBM patients with conventional prognostic factors
   [[40]12]. Accordingly, it is imperative to explore novel targeted
   progression and prognostic markers for GBM patients.

   Ras-associated binding (RAB) proteins constitute the largest family in
   the RAS superfamily of small GTPases, including over 60 identified
   members in humans [[41]13,[42]14]. RAB42 is a member of the RAB family.
   Aberrant expression of RABs is involved in the dysregulation of
   multiple signaling pathways and many diseases such as cancer,
   Alzheimer’s disease, and so on [[43]15,[44]16,[45]17]. In recent
   decades, many studies have documented that several RABs, such as RAB21
   [[46]18], RAB34 [[47]19], RAB14 [[48]20], and RAB27a [[49]21] are
   associated with the progression and prognosis of GBM and other tumors.
   However, there are few studies about RAB42 in cancers. It has been
   reported that RAB42 is negatively associated with 5-year overall
   survival and shows a poorer prognosis in glioma patients [[50]22].
   RAB42 is demonstrated to be involved in prenylation in vivo and in the
   cells [[51]23]. A study has suggested that in keratinocytes, RAB42
   participates in protein degradation on melanosomes [[52]24]. In
   addition, the potential effects of RAB42 in GBM development and
   prognosis have been seldom investigated as far as we know.

   Therefore, we herein aim to study the potential role of RAB42 in GBM
   through deep mining of publicly obtained GBM data and further
   experimental validation in our local specimens. Our findings are
   expected to give more references for the impacts of aberrant RAB42 in