title: Insight into the molecular basis of Schistosoma haematobium-induced bladder cancer through urine proteomics.
abstract: Infection due to Schistosoma haematobium is carcinogenic. However, the cellular and molecular mechanisms underlying urogenital schistosomiasis (UGS)-induced carcinogenesis have not been well defined. Conceptually, early molecular detection of this phenomenon, through non-invasive procedures, seems feasible and is desirable. Previous analysis of urine collected during UGS suggests that estrogen metabolites, including depurinating adducts, may be useful for this purpose. Here, a new direction was pursued: the identification of molecular pathways and potential biomarkers in S. haematobium-induced bladder cancer by analyzing the proteome profiling of urine samples from UGS patients. GeLC-MS/MS followed by protein-protein interaction analysis indicated oxidative stress and immune defense systems responsible for microbicide activity are the most representative clusters in UGS patients. Proteins involved in immunity, negative regulation of endopeptidase activity, and inflammation were more prevalent in UGS patients with bladder cancer, whereas proteins with roles in renal system process, sensory perception, and gas and oxygen transport were more abundant in subjects with urothelial carcinoma not associated with UGS. These findings highlighted a Th2-type immune response induced by S. haematobium, which seems to be further modulated by tumorigenesis, resulting in high-grade bladder cancer characterized by an inflammatory response and complement activation alternative pathway. These findings established a starting point for the development of multimarker strategies for the early detection of UGS-induced bladder cancer.
authors.affiliation: Experimental Pathology and Therapeutics Group - Research Center, Portuguese Oncology Institute - Porto (IPO-Porto), Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal.|Mass Spectrometry Group, QOPNA, Department of Chemistry, University of Aveiro, Campus Universitário de Santiago, 3810-193, Aveiro, Portugal.
authors.forename: Carina
authors.initials: C
authors.lastname: Bernardo
authors.affiliation: School of Health Sciences, University of Minho, Campus Gualtar, 4710-057, Braga, Portugal.
authors.forename: Maria Cláudia
authors.initials: MC
authors.lastname: Cunha
authors.affiliation: Experimental Pathology and Therapeutics Group - Research Center, Portuguese Oncology Institute - Porto (IPO-Porto), Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal.|Center for the Study of Animal Science, CECA/ICETA, University of Porto, Rua D. Manuel II, Apt 55142, 4051-401, Porto, Portugal.
authors.forename: Júlio Henrique
authors.initials: JH
authors.lastname: Santos
authors.affiliation: Center for the Study of Animal Science, CECA/ICETA, University of Porto, Rua D. Manuel II, Apt 55142, 4051-401, Porto, Portugal.|Center for Parasite Biology and Immunology (CIBP), National Institute of Health Dr. Ricardo Jorge (INSA), Rua Alexandro Herculano, 4000-055, Porto, Portugal.
authors.forename: José M Correia
authors.initials: JM
authors.lastname: da Costa
authors.affiliation: Department of Microbiology, Immunology & Tropical Medicine, and Research Center for Neglected Diseases of Poverty, School of Medicine & Health Sciences, George Washington University, Washington, DC, 20037, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Brindley
authors.affiliation: Experimental Pathology and Therapeutics Group - Research Center, Portuguese Oncology Institute - Porto (IPO-Porto), Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal.
authors.forename: Carlos
authors.initials: C
authors.lastname: Lopes
authors.affiliation: School of Health Sciences, University of Minho, Campus Gualtar, 4710-057, Braga, Portugal.
authors.forename: Francisco
authors.initials: F
authors.lastname: Amado
authors.affiliation: School of Health Sciences, University of Minho, Campus Gualtar, 4710-057, Braga, Portugal.
authors.forename: Rita
authors.initials: R
authors.lastname: Ferreira
authors.affiliation: Department of Medical Sciences, Institute for Biomedicine - iBiMED, University of Aveiro, Campus Universitário de Santiago, Agra do Crasto, 3810-193, Aveiro, Portugal.|Department of Physiology and Cardiothoracic Surgery, Faculty of Medicine, University of Porto, 4200-072, Porto, Portugal.
authors.forename: Rui
authors.initials: R
authors.lastname: Vitorino
authors.affiliation: Experimental Pathology and Therapeutics Group - Research Center, Portuguese Oncology Institute - Porto (IPO-Porto), Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal. llarasantos@gmail.com.|Department of Surgical Oncology, Portuguese Oncology Institute - Porto (IPO-Porto), Rua Dr. António Bernardino de Almeida, 4200-072, Porto, Portugal. llarasantos@gmail.com.
authors.forename: Lúcio Lara
authors.initials: LL
authors.lastname: Santos
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000818:Animals; D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000469:parasitology / Q000652:urine; D002471:Cell Transformation, Neoplastic / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D040901:Proteomics; D012548:Schistosoma haematobium; D012553:Schistosomiasis haematobia / Q000150:complications*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000469:parasitology / Q000652:urine; D055815:Young Adult
keywords: GeLC-MS/MS; Immune response; Squamous cell carcinoma; Urine proteomics; Urogenital schistosomiasis