Tumor Biology

, Volume 37, Issue 8, pp 11279–11287 | Cite as

Insight into the molecular basis of Schistosoma haematobium-induced bladder cancer through urine proteomics

  • Carina Bernardo
  • Maria Cláudia Cunha
  • Júlio Henrique Santos
  • José M. Correia da Costa
  • Paul J. Brindley
  • Carlos Lopes
  • Francisco Amado
  • Rita Ferreira
  • Rui Vitorino
  • Lúcio Lara Santos
Original Article

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.

Keywords

Urogenital schistosomiasis Immune response Squamous cell carcinoma GeLC-MS/MS Urine proteomics 

Notes

Acknowledgments

This work was supported by the Portuguese Foundation for Science and Technology (FCT), European Union, QREN, FEDER, and COMPETE for funding the QOPNA; by iBiMED research unit (project PEst-C/QUI/UI0062/2013, UID/BIM/04501/2013, UID/IC/00051/2013, and COST action BM1305) and PhD fellowship SFRH/BD/80855/2011 (CB); and by the Portuguese Mass Spectrometry Network (RNEM). The authors also acknowledge Clínica Sagrada Esperança and Serviço de Urologia do Hospital Américo Boavida from Luanda, Angola.

Compliance with ethical standards

Urine samples were obtained according to a collaborative program between Clínica da Sagrada Esperança, Américo Boavida University Hospital and IPO-Porto after obtaining informed consent from all participants. This study was approved by the local ethics committee and followed the Declaration of Helsinki.

Conflicts of interest

None

Supplementary material

13277_2016_4997_MOESM1_ESM.doc (136 kb)
Supplementary Figure S1 (DOC 135 kb)
13277_2016_4997_MOESM2_ESM.doc (232 kb)
Supplementary Figure S2 (DOC 232 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Carina Bernardo
    • 1
    • 2
  • Maria Cláudia Cunha
    • 3
  • Júlio Henrique Santos
    • 1
    • 4
  • José M. Correia da Costa
    • 4
    • 5
  • Paul J. Brindley
    • 6
  • Carlos Lopes
    • 1
  • Francisco Amado
    • 3
  • Rita Ferreira
    • 3
  • Rui Vitorino
    • 7
    • 8
  • Lúcio Lara Santos
    • 1
    • 9
  1. 1.Experimental Pathology and Therapeutics Group - Research CenterPortuguese Oncology Institute - Porto (IPO-Porto)PortoPortugal
  2. 2.Mass Spectrometry Group, QOPNA, Department of ChemistryUniversity of AveiroAveiroPortugal
  3. 3.School of Health SciencesUniversity of MinhoBragaPortugal
  4. 4.Center for the Study of Animal Science, CECA/ICETAUniversity of PortoPortoPortugal
  5. 5.Center for Parasite Biology and Immunology (CIBP)National Institute of Health Dr. Ricardo Jorge (INSA)PortoPortugal
  6. 6.Department of Microbiology, Immunology & Tropical Medicine, and Research Center for Neglected Diseases of Poverty, School of Medicine & Health SciencesGeorge Washington UniversityWashingtonUSA
  7. 7.Department of Medical Sciences, Institute for Biomedicine – iBiMEDUniversity of AveiroAveiroPortugal
  8. 8.Department of Physiology and Cardiothoracic Surgery, Faculty of MedicineUniversity of PortoPortoPortugal
  9. 9.Department of Surgical OncologyPortuguese Oncology Institute - Porto (IPO-Porto)PortoPortugal

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