Investigating the dysfunctional pathogenesis of Wilms’ tumor through a multidimensional integration strategy

Wenbiao Chen, Jia Zhuang, Lan Gong, Yong Dai, Hongyan Diao


Background: Wilms’ tumor (WT) is a common kidney tumor in early childhood which is characterized by multiple congenital anomalies and syndromes. With the continuous improvement of medical standards, the cure rate and survival period of WT have increased. However, its molecular mechanism is still elusive.
Methods: A comprehensive multidimensional integration strategy was used to comprehensively analyze the mechanisms of WT.
Results: By integrating the potential pathogenic genes of kidney cancer and performing co-expression analysis on the disease-related genes, 23 functional modules were obtained. All the genes were differentially expressed in WT, and were mainly involved in many biological processes and signaling pathways, such as Wnt/β-catenin, mTOR/ERK and calcineurin. Additionally, based on the relationship between transcriptional and post-transcriptional regulatory systems, in functional modules, transcription factors (TFs) including STAT3, HDAC1 and SP1 as well as non-coding RNAs (ncRNAs) such as miR-335-5p, miR-21-5p and TUG1 were identified. Finally, potential drugs for these multifactor regulated dysfunctional modules which may have certain pharmacological or toxicological effects on WT such as cisplatin, sorafenib, and zinc were predicted.
Conclusions: A multidimensional dysfunction mechanism, involving disease-related genes, TFs and ncRNAs was revealed in the pathogenesis of WT. Functional modules were used to predict potential drugs which can be used in personalized therapy and drug delivery. This study explored the pathogenesis of WT from a new perspective, and provides new candidate targets and therapeutic drugs for improving the cure rate of WT.