RNA Sequencing and Bioinformatic Analysis on Retinoblastoma Revealing Cell Cycle Deregulation being a Key Process in Retinoblastoma Tumorigenesis

PURPOSE: Retinoblastoma is a primary pediatric ocular malignancy that could be fatal with inadequate treatment. Whilst multimodal treatments are applied for eye salvage, yet vision loss and metastasis could occur in some patients. The present study aims to explore key pathways and factors in retinoblastoma pathogenesis, which could be potential targets for novel therapies of retinoblastoma treatments. METHODS: RNA sequencing was performed on three retinoblastoma tissues and referenced with three normal retinas. Differentially-expressed genes (DEGs) were identified from sequencing data, and further analyzed with clustering analysis, function and pathway enrichment, protein-protein interaction (PPI), and data-mining analysis in order to screen for tumorigenic relevancy. RESULTS: A total of 331 DEGs were identified by clustering analysis of retinoblastoma tissues, and the expression patterns were significantly distinguishable from normal retinas. Function and pathway enrichment and PPI analysis together showed that cell cycle was the most prominently upregulated pathway found in retinoblastoma tissues. Following comprehensive bioinformatic analyses, six key genes relevant to cell cycle regulation were identified, namely BUB1, RRM2, TPX2, UBE2C, NUSAP1 and DTL. CONCLUSIONS: Cell cycle pathway and six relevant genes may be potential key factors in retinoblastoma tumorigenesis, and laying foundation for prospective investigation on development of novel targeted therapies.