Literature Data Mining and Enrichment Analysis Reveal a Genetic Network of 423 Genes for Renal Cancer

Background: Renal cancer (RC) originates in the cells of the kidneys. Worldwide, approximately 208,500 new cases of renal cancer are diagnosed annually. This accounts for just under 2 % of all cancers. Those with a family history of RC have an increased risk of developing the disease. Recent research has identified hundreds of genes which may relate to its development. No study has systematically summarized these findings or provided an objective view of the genes reportedly associated with RC.Methods: Literature data mining (LDM) was performed on more than 1,100 articles for publications between 1988 and April 2016 in which 423 genes were reported to be RC-associated. A gene set enrichment analysis (GSEA) and a sub-network enrichment analysis (SNEA) were performed to study the functional profile and pathogenic significance of these genes. A network connectivity analysis (NCA) to study the associations between the reported genes was done. Literature, and enrichment metrics, analyses were used to identify genes with specific RC significance.Results: Multiple RC associations for 329 of the 423 genes enriched 100 pathways (p < 1.2e-10) were demonstrated. Ten genes (IL6, VEGFA, HIF1A, EGFR, PTEN, TP53, FGF2, CTNNB1, HMOX1, and BRCA1) were identified as having the most significant association with RC in terms of both functional diversity and replication frequency. Three novel genes, CD274, NOTCH1, and CREB1, were found to play roles within many significant RC-related pathways, warranting their further study. SNEA, and, NCA results indicated that many of these genes work as a functional network that plays roles in the RC-related disorder pathogeneses.Conclusion: The results suggest that the genetic causes of RC are linked to a genetic network composed of a large number of genes. The gene lists, together with the literature, and enrichment, metrics provided by this study, may serve a basis for further biological and genetic studies in the field.