title: Temporal Identification of Dysregulated Genes and Pathways in Clear Cell Renal Cell Carcinoma Based on Systematic Tracking of Disrupted Modules.
abstract: OBJECTIVE
  The objective of this work is to identify dysregulated genes and pathways of ccRCC temporally according to systematic tracking of the dysregulated modules of reweighted Protein-Protein Interaction (PPI) networks.
  
  
  METHODS
  Firstly, normal and ccRCC PPI network were inferred and reweighted based on Pearson correlation coefficient (PCC). Then, we identified altered modules using maximum weight bipartite matching and ranked them in nonincreasing order. Finally, gene compositions of altered modules were analyzed, and pathways enrichment analyses of genes in altered modules were carried out based on Expression Analysis Systematic Explored (EASE) test.
  
  
  RESULTS
  We obtained 136, 576, 693, and 531 disrupted modules of ccRCC stages I, II, III, and IV, respectively. Gene composition analyses of altered modules revealed that there were 56 common genes (such as MAPK1, CCNA2, and GSTM3) existing in the four stages. Besides pathway enrichment analysis identified 5 common pathways (glutathione metabolism, cell cycle, alanine, aspartate, and glutamate metabolism, arginine and proline metabolism, and metabolism of xenobiotics by cytochrome P450) across stages I, II, III, and IV.
  
  
  CONCLUSIONS
  We successfully identified dysregulated genes and pathways of ccRCC in different stages, and these might be potential biological markers and processes for treatment and etiology mechanism in ccRCC.
authors.affiliation: Center for Kidney Disease, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, China.
authors.forename: Shao-Mei
authors.initials: SM
authors.lastname: Wang
authors.affiliation: Department of Urinary Surgery, Qianfoshan Hospital Affiliated to Shandong University, 16766 Jingshi Road, Jinan, Shandong 250014, China.
authors.forename: Ze-Qiang
authors.initials: ZQ
authors.lastname: Sun
authors.affiliation: Department of Urinary Surgery, Qianfoshan Hospital Affiliated to Shandong University, 16766 Jingshi Road, Jinan, Shandong 250014, China.
authors.forename: Hong-Yun
authors.initials: HY
authors.lastname: Li
authors.affiliation: Department of Urinary Surgery, Qianfoshan Hospital Affiliated to Shandong University, 16766 Jingshi Road, Jinan, Shandong 250014, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Urinary Surgery, Qianfoshan Hospital Affiliated to Shandong University, 16766 Jingshi Road, Jinan, Shandong 250014, China.
authors.forename: Qing-Yong
authors.initials: QY
authors.lastname: Liu
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019295:Computational Biology; D030541:Databases, Genetic / Q000706:statistics & numerical data; D015972:Gene Expression Regulation, Neoplastic; D053263:Gene Regulatory Networks; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D060066:Protein Interaction Maps / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor