Title:Contextualizing the Genes Altered in Bladder Neoplasms in Pediatric and Teen Patients Allows Identifying Two Main Classes of Biological Processes Involved and New Potential Therapeutic Targets
Volume: 17
Issue: 1
Author(s): A. Porrello and R. Piergentili
Affiliation:
Keywords:
Bioinformatics, biomedical modeling, gene set, neoplastic transformation, PubMed query.
Abstract: Research on bladder neoplasms in pediatric and teen patients (BNPTP) has
described 21 genes, which are variously involved in this disease and are mostly responsible
for deregulated cell proliferation. However, due to the limited number of
publications on this subject, it is still unclear what type of relationships there are
among these genes and which are the chances that, while having different molecular
functions, they i) act as downstream effector genes of well-known pro- or anti- proliferative stimuli and/or interplay with
biochemical pathways having oncological relevance or ii) are specific and, possibly, early biomarkers of these pathologies.
A Gene Ontology (GO)-based analysis showed that these 21 genes are involved in biological processes, which can
be split into two main classes: cell regulation-based and differentiation/development-based. In order to understand the involvement/
overlapping with main cancer-related pathways, we performed a meta-analysis dependent on the 189 oncogenic
signatures of the Molecular Signatures Database (OSMSD) curated by the Broad Institute. We generated a binary
matrix with 53 gene signatures having at least one hit; this analysis i) suggests that some genes of the original list show
inconsistencies and might need to be experimentally re- assessed or evaluated as biomarkers (in particular, ACTA2) and
ii) allows hypothesizing that important (proto)oncogenes (E2F3, ERBB2/HER2, CCND1, WNT1, and YAP1) and (putative)
tumor suppressors (BRCA1, RBBP8/CTIP, and RB1-RBL2/p130) may participate in the onset of this disease or
worsen the observed phenotype, thus expanding the list of possible molecular targets for the treatment of BNPTP.
