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

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.

Building the drug-GO function network to screen significant candidate drugs for myasthenia gravis

“…According to a novel form of network-based gene enrichment, Lena et al proposed a more effective method for detecting BPs associated diseases [10], which may help us to better understand the mechanism of different diseases if we can determine the BPs of diseases. Another study has found that altered genes in bladder neoplasm patients were mainly enriched for two classes of BP through GO analysis, which suggests that these BPs may participate in the onset of this disease or worsen the observed phenotype [11]. In addition, Wirapati et al discovered that the GO-BPs with high ‘coexpression’ genes could help to reveal the common thread connecting molecular subtyping and several prognostic signatures of breast cancer [12].…”

“…Researchers have proposed a method for drug repositioning based on disease-associated GO-BP [17]. Meanwhile, Porrelloa and Piergentilib identified new potential therapeutic targets for bladder neoplasm by analyzing BP in which altered genes were enriched [11], which provided strong support for screening new drugs based on GO-BP. However, no studies have focused on the association between drugs and GO-BPs in MG.…”