Investigation of Extracellular Vesicles miRNA Prognostic Biomarkers in Human Retinoblastoma
Ahmad Bereimipour1 , Sara Taleahmad2 , Leila Satarian1 *
- Department of Stem Cells Biology and Technology, Cell Science Research Center, Royan Institute for Stem Cell. Biology and Technology, ACECR, Tehran, Iran
- Department of Molecular Systems Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, P.O. Box 19395-4644, Tehran, Iran
Abstract: Retinoblastoma is a common intraocular cancer in infants and children. Although the cause of this disease is a mutation in the RB1 gene, the cancerous mass formed in different patients is seen in non-invasive states, limited to the ocular cavity or invasive state distributed to other parts of the body it is impossible to predict this tumor's aggressive form in the early stages of the disease, so systemic chemotherapy is performed using a combination of several drugs as the primary treatment for these patients(1–3). Separation and identification of non-invasive and invasive types of tumors will be effective in managing treatment and reducing the side effects of chemical drugs(4,5). Accordingly, some diagnostic biomarkers were investigated in this study by separating miRNAs in the blood serum extracellular vesicles of invasive and non-invasive retinoblastoma patients.
Methods: We have specified the differentially expressed genes (DEGs) extracted from GEO microarray datasets of miRNAs serum (GSE41321) and retinoblastoma tissue (GSE7072). Then, isolated shared miRNAs between serum and RB tumor tissue via Venn diagram. After that, evaluated signaling pathways and the gene ontology of target genes to determine best functional miRNAs in retinoblastoma. Finally, assessed miRNAs in Exocarta and vesicle pedia databases for extracellular vesicles existence
Results: First, miRNAs were shared between serum and retinoblastoma tumor tissue. Based on this, 14 high-expression miRNAs and 7 low-expression miRNAs were obtained Collectively. Based on the common genes of miRNAs with differential genes between invasive and non-invasive retinoblastoma, miR-181, miR-135a, miR-20a, miR-373, and miR-191 were selected. These miRNAs were then examined in the extracellular vesicles the results indicated that miR-144, 99a, 191, and 20a were present in extracellular vesicles of serum and tissue of retinoblastoma based on adjusted p value and literature review
Conclusion: Through integrated and regular bioinformatics analyses, we found crucial miRNAs by examining patients' serum samples, which can play an essential role in determining patients with non-invasive retinoblastoma. The results of this study showed that miR-144, 99a, 191, and 20a are suitable options in distinguishing based on extracellular vesicles study between non-invasive and invasive retinoblastoma, which are suggested for further evaluation.
