Cargando…
P53 and Cancer-Associated Sialylated Glycans Are Surrogate Markers of Cancerization of the Bladder Associated with Schistosoma haematobium Infection
BACKGROUND: Bladder cancer is a significant health problem in rural areas of Africa and the Middle East where Schistosoma haematobium is prevalent, supporting an association between malignant transformation and infection by this blood fluke. Nevertheless, the molecular mechanisms linking these event...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4263606/ https://www.ncbi.nlm.nih.gov/pubmed/25502795 http://dx.doi.org/10.1371/journal.pntd.0003329 |
_version_ | 1782348607178932224 |
---|---|
author | Santos, Júlio Fernandes, Elisabete Ferreira, José Alexandre Lima, Luís Tavares, Ana Peixoto, Andreia Parreira, Beatriz Correia da Costa, José Manuel Brindley, Paul J. Lopes, Carlos Santos, Lúcio L. |
author_facet | Santos, Júlio Fernandes, Elisabete Ferreira, José Alexandre Lima, Luís Tavares, Ana Peixoto, Andreia Parreira, Beatriz Correia da Costa, José Manuel Brindley, Paul J. Lopes, Carlos Santos, Lúcio L. |
author_sort | Santos, Júlio |
collection | PubMed |
description | BACKGROUND: Bladder cancer is a significant health problem in rural areas of Africa and the Middle East where Schistosoma haematobium is prevalent, supporting an association between malignant transformation and infection by this blood fluke. Nevertheless, the molecular mechanisms linking these events are poorly understood. Bladder cancers in infected populations are generally diagnosed at a late stage since there is a lack of non-invasive diagnostic tools, hence enforcing the need for early carcinogenesis markers. METHODOLOGY/PRINCIPAL FINDINGS: Forty-three formalin-fixed paraffin-embedded bladder biopsies of S. haematobium-infected patients, consisting of bladder tumours, tumour adjacent mucosa and pre-malignant/malignant urothelial lesions, were screened for bladder cancer biomarkers. These included the oncoprotein p53, the tumour proliferation rate (Ki-67>17%), cell-surface cancer-associated glycan sialyl-Tn (sTn) and sialyl-Lewis(a/x) (sLe(a)/sLe(x)), involved in immune escape and metastasis. Bladder tumours of non-S. haematobium etiology and normal urothelium were used as controls. S. haematobium-associated benign/pre-malignant lesions present alterations in p53 and sLe(x) that were also found in bladder tumors. Similar results were observed in non-S. haematobium associated tumours, irrespectively of their histological nature, denoting some common molecular pathways. In addition, most benign/pre-malignant lesions also expressed sLe(a). However, proliferative phenotypes were more prevalent in lesions adjacent to bladder tumors while sLe(a) was characteristic of sole benign/pre-malignant lesions, suggesting it may be a biomarker of early carcionogenesis associated with the parasite. A correlation was observed between the frequency of the biomarkers in the tumor and adjacent mucosa, with the exception of Ki-67. Most S. haematobium eggs embedded in the urothelium were also positive for sLe(a) and sLe(x). Reinforcing the pathologic nature of the studied biomarkers, none was observed in the healthy urothelium. CONCLUSION/SIGNIFICANCE: This preliminary study suggests that p53 and sialylated glycans are surrogate biomarkers of bladder cancerization associated with S. haematobium, highlighting a missing link between infection and cancer development. Eggs of S. haematobium express sLe(a) and sLe(x) antigens in mimicry of human leukocytes glycosylation, which may play a role in the colonization and disease dissemination. These observations may help the early identification of infected patients at a higher risk of developing bladder cancer and guide the future development of non-invasive diagnostic tests. |
format | Online Article Text |
id | pubmed-4263606 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-42636062014-12-19 P53 and Cancer-Associated Sialylated Glycans Are Surrogate Markers of Cancerization of the Bladder Associated with Schistosoma haematobium Infection Santos, Júlio Fernandes, Elisabete Ferreira, José Alexandre Lima, Luís Tavares, Ana Peixoto, Andreia Parreira, Beatriz Correia da Costa, José Manuel Brindley, Paul J. Lopes, Carlos Santos, Lúcio L. PLoS Negl Trop Dis Research Article BACKGROUND: Bladder cancer is a significant health problem in rural areas of Africa and the Middle East where Schistosoma haematobium is prevalent, supporting an association between malignant transformation and infection by this blood fluke. Nevertheless, the molecular mechanisms linking these events are poorly understood. Bladder cancers in infected populations are generally diagnosed at a late stage since there is a lack of non-invasive diagnostic tools, hence enforcing the need for early carcinogenesis markers. METHODOLOGY/PRINCIPAL FINDINGS: Forty-three formalin-fixed paraffin-embedded bladder biopsies of S. haematobium-infected patients, consisting of bladder tumours, tumour adjacent mucosa and pre-malignant/malignant urothelial lesions, were screened for bladder cancer biomarkers. These included the oncoprotein p53, the tumour proliferation rate (Ki-67>17%), cell-surface cancer-associated glycan sialyl-Tn (sTn) and sialyl-Lewis(a/x) (sLe(a)/sLe(x)), involved in immune escape and metastasis. Bladder tumours of non-S. haematobium etiology and normal urothelium were used as controls. S. haematobium-associated benign/pre-malignant lesions present alterations in p53 and sLe(x) that were also found in bladder tumors. Similar results were observed in non-S. haematobium associated tumours, irrespectively of their histological nature, denoting some common molecular pathways. In addition, most benign/pre-malignant lesions also expressed sLe(a). However, proliferative phenotypes were more prevalent in lesions adjacent to bladder tumors while sLe(a) was characteristic of sole benign/pre-malignant lesions, suggesting it may be a biomarker of early carcionogenesis associated with the parasite. A correlation was observed between the frequency of the biomarkers in the tumor and adjacent mucosa, with the exception of Ki-67. Most S. haematobium eggs embedded in the urothelium were also positive for sLe(a) and sLe(x). Reinforcing the pathologic nature of the studied biomarkers, none was observed in the healthy urothelium. CONCLUSION/SIGNIFICANCE: This preliminary study suggests that p53 and sialylated glycans are surrogate biomarkers of bladder cancerization associated with S. haematobium, highlighting a missing link between infection and cancer development. Eggs of S. haematobium express sLe(a) and sLe(x) antigens in mimicry of human leukocytes glycosylation, which may play a role in the colonization and disease dissemination. These observations may help the early identification of infected patients at a higher risk of developing bladder cancer and guide the future development of non-invasive diagnostic tests. Public Library of Science 2014-12-11 /pmc/articles/PMC4263606/ /pubmed/25502795 http://dx.doi.org/10.1371/journal.pntd.0003329 Text en © 2014 Santos et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Santos, Júlio Fernandes, Elisabete Ferreira, José Alexandre Lima, Luís Tavares, Ana Peixoto, Andreia Parreira, Beatriz Correia da Costa, José Manuel Brindley, Paul J. Lopes, Carlos Santos, Lúcio L. P53 and Cancer-Associated Sialylated Glycans Are Surrogate Markers of Cancerization of the Bladder Associated with Schistosoma haematobium Infection |
title | P53 and Cancer-Associated Sialylated Glycans Are Surrogate Markers of Cancerization of the Bladder Associated with Schistosoma haematobium Infection |
title_full | P53 and Cancer-Associated Sialylated Glycans Are Surrogate Markers of Cancerization of the Bladder Associated with Schistosoma haematobium Infection |
title_fullStr | P53 and Cancer-Associated Sialylated Glycans Are Surrogate Markers of Cancerization of the Bladder Associated with Schistosoma haematobium Infection |
title_full_unstemmed | P53 and Cancer-Associated Sialylated Glycans Are Surrogate Markers of Cancerization of the Bladder Associated with Schistosoma haematobium Infection |
title_short | P53 and Cancer-Associated Sialylated Glycans Are Surrogate Markers of Cancerization of the Bladder Associated with Schistosoma haematobium Infection |
title_sort | p53 and cancer-associated sialylated glycans are surrogate markers of cancerization of the bladder associated with schistosoma haematobium infection |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4263606/ https://www.ncbi.nlm.nih.gov/pubmed/25502795 http://dx.doi.org/10.1371/journal.pntd.0003329 |
work_keys_str_mv | AT santosjulio p53andcancerassociatedsialylatedglycansaresurrogatemarkersofcancerizationofthebladderassociatedwithschistosomahaematobiuminfection AT fernandeselisabete p53andcancerassociatedsialylatedglycansaresurrogatemarkersofcancerizationofthebladderassociatedwithschistosomahaematobiuminfection AT ferreirajosealexandre p53andcancerassociatedsialylatedglycansaresurrogatemarkersofcancerizationofthebladderassociatedwithschistosomahaematobiuminfection AT limaluis p53andcancerassociatedsialylatedglycansaresurrogatemarkersofcancerizationofthebladderassociatedwithschistosomahaematobiuminfection AT tavaresana p53andcancerassociatedsialylatedglycansaresurrogatemarkersofcancerizationofthebladderassociatedwithschistosomahaematobiuminfection AT peixotoandreia p53andcancerassociatedsialylatedglycansaresurrogatemarkersofcancerizationofthebladderassociatedwithschistosomahaematobiuminfection AT parreirabeatriz p53andcancerassociatedsialylatedglycansaresurrogatemarkersofcancerizationofthebladderassociatedwithschistosomahaematobiuminfection AT correiadacostajosemanuel p53andcancerassociatedsialylatedglycansaresurrogatemarkersofcancerizationofthebladderassociatedwithschistosomahaematobiuminfection AT brindleypaulj p53andcancerassociatedsialylatedglycansaresurrogatemarkersofcancerizationofthebladderassociatedwithschistosomahaematobiuminfection AT lopescarlos p53andcancerassociatedsialylatedglycansaresurrogatemarkersofcancerizationofthebladderassociatedwithschistosomahaematobiuminfection AT santosluciol p53andcancerassociatedsialylatedglycansaresurrogatemarkersofcancerizationofthebladderassociatedwithschistosomahaematobiuminfection |