Exploration of retinoblastoma pathogenesis with bioinformatics

Abstract

Background: Differentially expressed genes (DEGs) from retinoblastoma (RB) tissues play key roles in the progression of RB. However, the role of DEGs in different subtypes and stages of RB has not yet been systematically analyzed.Methods: In this study, the DEGs for tumor and adjacent from 3 RB data sets GSE24673, GSE97508, and GSE110811 were analyzed with regard to the different subtypes and stages of the disease.Results: Through comparison with adjacent tissues, a total of 78 upregulated genes and 155 downregulated genes from the RB tissues were identified across the 3 data sets. Gene set enrichment analysis (GSEA) showed that the 3 representative genes CDK1, CDC20, and BUB1, which were all upregulated, could promote the cell cycle in RB. Compared with adjacent tissues in GSE97508, a total of 19 gigantol-targeted genes were predicted to be upregulated in invasive RB tissues. On the other hand, DEGs for tumor and adjacent from 3 RB data sets GSE24673, GSE97508, and GSE110811 were integrated with regard to invasiveness and stages of the disease, and another 19 DEGs were subsequently identified. Among these genes, UHRF1 was the only identified upregulated gene, while the other 18 were all downregulated genes. Cell Counting Kit-8 (CCK-8) experiment and GSEA results showed that UHRF1 can promote the proliferation and invasion of RB.Conversely, the downregulated representative gene CADM1 is a tumor suppressor gene, which can inhibit the progression of RB.Conclusions: This study indicated that the verified DEGs are continuously and consistently expressed in different subtypes and stages of RB. These DEGs may be the key to understanding the development and invasion of RB.

Identifying Treatment Resistance Related Pathways by Analyzing Serum Extracellular Vesicles of Patients With Resistant Versus Regressed Retinoblastoma

“…Previous microarray and bioinformatics analysis on RB tumor specimens revealed that the above enriched terms were associated with RB tumor occurrence, development, and chemo-resistance by regulating cell growth, cell survival, and proliferation. 22 , 29 , 30 Several studies have demonstrated that the neuroactive ligand–receptor interaction pathway is linked to a poor prognosis in various cancers, and breast cancer patients with low expression of cannabinoid receptor 1 (CNR1, part of this pathway) may benefit from chemotherapy. 31 Bioinformatics analysis of gene expression data of RB tumor tissues compared to normal retina revealed that the aberrantly expressed protein coding genes and target genes for DE lncRNAs are enriched for neuroactive ligand–receptor interaction.…”

“… 31 Bioinformatics analysis of gene expression data of RB tumor tissues compared to normal retina revealed that the aberrantly expressed protein coding genes and target genes for DE lncRNAs are enriched for neuroactive ligand–receptor interaction. 29 , 30 Moreover, this is one of the 50 pathways significantly enriched for DEGs between chemoresistance Y79 versus parental Y79 cells. 32 MicroRNAs in cancer were enriched only for DE genes of TR-RB.…”

The UHRF protein family in epigenetics, development, and carcinogenesis

“…Multiple reports have described the upregulation of UHRF1 in cancer cells (Table 1 ). 99 – 106 ) Because higher expression is often correlated with more advanced cancer stages, multiple metastases, and/or poor prognosis, UHRF1 has been suggested as a good biomarker for various malignancies. 99 ) In addition, because UHRF1 expression is limited to proliferating cells, inhibitors of UHRF1 may be ideal candidates for anticancer drugs that could act across a broad spectrum of cancer types, with minimal adverse effects.…”