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

Purpose: Retinoblastoma (RB) is a primary pediatric ocular malignancy that can be fatal with inadequate treatment. While multimodal treatments are applied for eye salvage, vision loss and metastasis can occur in some patients. The present study aimed to explore key pathways and factors in RB pathogenesis, which could be potential targets for novel RB treatments. Methods: RNA sequencing was performed on three RB 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 RB 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 RB 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 RB tumorigenesis and laying the foundation for prospective investigation on development of novel targeted therapies.