title: Heterogeneity research in muscle-invasive bladder cancer based on differential protein expression analysis.
abstract: The aim of this study was to study the expression profiles of muscle-invasive bladder cancer (MIBC) cells of different risk groups and to explore the crucial role of biological pathway change in heterogeneity of MIBC cells. Thirty individual samples (cancer and non-cancerous specimens) were obtained from patients with MIBC. Laser capture microdissection was employed to harvest the homogeneous MIBC cells and normal urothelial cells. iTRAQ and 2D-LC-MS/MS were used to quantify and identify the differently expressed proteins. Then, the significantly changed proteins were further analyzed using Arraytrack ™ software. The interested proteins were compared with the published literatures to discuss the exact functions. A total of 3,073 non-redundant proteins were identified in this research; therefore, 855/2,210/633 (fold change >1.5 relative to normal group) presented in high-/median-/low-risk groups, respectively. 617/1,620/463 proteins with SWISS-ACC number output from Arraytrack ™ software and presented in high-/median-/low-risk groups, respectively. Pathway analysis revealed that the mainly changed pathways (top-10, p < 0.05) in Genetic information processing category were similar in high- and median-risk groups, including Kyoto Encyclopedia of Genes and Genomes (KEGG) spliceosome, protein export, ribosome pathways. The mainly altered pathways in Metabolism category included glycolysis/gluconeogenesis, pentose phosphate, pyruvate metabolism pathway for high-risk group, and glutathione metabolism, citrate cycle, oxidative phosphorylation pathways for median-risk group. The major changed pathways for low-risk group included focal adhesion pathway and ECM-receptor interaction pathway. The changed biological pathways are closely related to the regulation of heterogeneity for MIBC. The KEGG pathways of Genetic information processing category and Metabolism (anaerobic or aerobic) category play a crucial role in determining the malignant phenotype of MIBC cells. The quantification analysis of proteins combining with the KEGG pathway analysis contributes to screening candidate biomarkers and guides the biological molecular therapy of MIBC.
authors.affiliation: Department of Urology, The Affiliated Hospital of Qingdao University, LaoShan District, 59 Haier Road, Qingdao, 266101, China.
authors.forename: Peng Fei
authors.initials: PF
authors.lastname: Liu
authors.forename: Yan Wei
authors.initials: YW
authors.lastname: Cao
authors.forename: Hai Ping
authors.initials: HP
authors.lastname: Jiang
authors.forename: Yong Hua
authors.initials: YH
authors.lastname: Wang
authors.forename: Xue Cheng
authors.initials: XC
authors.lastname: Yang
authors.forename: Xin Sheng
authors.initials: XS
authors.lastname: Wang
authors.forename: Hai Tao
authors.initials: HT
authors.lastname: Niu
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D002853:Chromatography, Liquid; D030562:Databases, Protein; D006801:Humans; D061346:Laser Capture Microdissection; D053858:Metabolic Networks and Pathways; D020543:Proteome / Q000032:analysis*; D040901:Proteomics / Q000379:methods*; D053719:Tandem Mass Spectrometry; D001749:Urinary Bladder Neoplasms / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology; D019459:Urothelium / Q000737:chemistry* / Q000378:metabolism / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D020543:Proteome
references.citation: Cell. 2008 May 16;133(4):704-15
references.pmid: 18485877
references.citation: Br J Cancer. 2013 Jul 9;109(1):14-23
references.pmid: 23764751
references.citation: Urology. 2007 Sep;70(3):602-7
references.pmid: 17688917
references.citation: Am J Physiol Endocrinol Metab. 2013 Apr 15;304(8):E789-99
references.pmid: 23403946
references.citation: Mol Cell Biochem. 2012 Nov;370(1-2):127-39
references.pmid: 22868929
references.citation: Chemotherapy. 2007;53(4):233-56
references.pmid: 17595539
references.citation: Tumour Biol. 2013 Feb;34(1):25-31
references.pmid: 22961700
references.citation: Cancer Res. 2007 Apr 1;67(7):3345-55
references.pmid: 17409444
references.citation: Clin Cancer Res. 2009 Jan 1;15(1):22-9
references.pmid: 19118029
references.citation: Nat Cell Biol. 2007 Aug;9(8):858-67
references.pmid: 17671451
references.citation: Mutat Res. 2004 May 18;549(1-2):241-53
references.pmid: 15120974
references.citation: Med Oncol. 2013;30(2):587
references.pmid: 23609195
references.citation: Cell. 2005 Oct 7;123(1):49-63
references.pmid: 16213212
references.citation: Cancer Cell Int. 2012 Aug 25;12(1):39
references.pmid: 22920603
references.citation: IUBMB Life. 2013 Nov;65(11):904-10
references.pmid: 24265197
references.citation: Mol Biol Rep. 2012 Mar;39(3):3109-15
references.pmid: 21750916
references.citation: Pathol Oncol Res. 2014 Apr;20(2):263-6
references.pmid: 23999979
references.citation: Am J Pathol. 2002 Feb;160(2):693-700
references.pmid: 11839590
references.citation: EMBO Rep. 2013 Aug;14(8):686-95
references.pmid: 23846313
references.citation: FEBS Lett. 2012 Feb 17;586(4):356-61
references.pmid: 22245673
references.citation: CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90
references.pmid: 21296855
references.citation: Am J Clin Oncol. 2011 Dec;34(6):628-35
references.pmid: 20805739
references.citation: Clin Cancer Res. 2014 May 15;20(10):2595-606
references.pmid: 24634381
references.citation: CA Cancer J Clin. 2014 Jan-Feb;64(1):9-29
references.pmid: 24399786