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

Background: Renal cancer (RC) is a type of cancer that starts in the cells of the kidneys. Around 208,500 new cases of renal cancer worldwide are diagnosed yearly, accounting for just under 2% of all cancers. People who have a family history of RC have an increased risk of developing the disease. Recent years, an increased number of researches have been reported hundreds of genes related to the development of the disease. However, no systemic study has summarized these findings and has provided an objective view of these genes reportedly associated with RC. Methods: We conducted a literature data mining (LDM) of over 1,100 articles covering publications from 1988 to April 2016, where 423 genes were reported to be associated with RC. We then performed a gene set enrichment analysis (GSEA) and a sub-network enrichment analysis (SNEA) to study the functional profile and pathogenic significance of these genes with RC. Lastly, we performed a network connectivity analysis (NCA) to study the associations between the reported genes. Literature and enrichment metrics analyses were used to discover genes with specific significance to the disease. Results: 329/423 genes enriched 100 pathways (p<1.2e-10), demonstrating multiple associations with RC. Ten genes (IL6, VEGFA, HIF1A, EGFR, PTEN, TP53, FGF2, CTNNB1, HMOX1, and BRCA1) were identified as the top genes associated with leukemia in terms of both functional diversity and replication frequency. Additionally, three novel genes, CD274, NOTCH1, and CREB1, were found to play roles within many significant RC related pathways, suggesting that they were worthy of further study. Moreover, SNEA and NCA results indicated that many of these genes work as a functional network that plays roles in the pathogenesis of other RC related disorders. Conclusion: Our results suggest that the genetic causes of RC were linked to a genetic network composed of a large group of genes. The gene lists, together with the literature and enrichment metrics provided in this study, can serve as a groundwork for further biological/genetic studies in the field.