Wenbiao Chen1, Jia Zhuang2, Lan Gong3, Yong Dai4, Hongyan Diao1. 1. State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China. 2. Department of Urinary Surgery, Puning People's Hospital Affiliated to Southern Medical University, Jieyang 515300, China. 3. Microbiome Research Centre, St George and Sutherland Clinical School, University of New South Wales, Sydney, NSW, Australia. 4. Clinical Medical Research Center, Shenzhen People's Hospital, The Second Clinical Medical College of Jinan University, Shenzhen 518020, China.
Abstract
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.
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.
Authors: Qianghua Hu; Fei Gao; Weihua Tian; E Cristy Ruteshouser; Yaqing Wang; Alexander Lazar; John Stewart; Louise C Strong; Richard R Behringer; Vicki Huff Journal: J Clin Invest Date: 2010-12-01 Impact factor: 14.808