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Article

Application of Proteogenomics to Urine Analysis towards the Identification of Novel Biomarkers of Prostate Cancer: An Exploratory Study

1
Department of Medical Sciences, Institute of Biomedicine-iBiMED, University of Aveiro, 3810-193 Aveiro, Portugal
2
Cancer Biology and Epigenetics Group, Research Center of Portuguese Oncology Institute of Porto (GEBC CI-IPOP) & Porto Comprehensive Cancer Center (P.CCC), 4200-072 Porto, Portugal
3
[email protected], Department of Surgery and Physiology, Faculty of Medicine of the University of Porto, 4200-319 Porto, Portugal
4
LAQV/REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal
5
Department of Pathology, Portuguese Oncology Institute of Porto (IPO Porto) & Porto Comprehensive Cancer Center (P.CCC), 4200-072 Porto, Portugal
6
Department of Pathology and Molecular Immunology, Institute of Biomedical Sciences Abel Salazar, University of Porto (ICBAS-UP), 4050-513 Porto, Portugal
7
Department of Clinical Pathology, Portuguese Oncology Institute of Porto (IPO Porto) & Porto Comprehensive Cancer Center (P.CCC), 4200-072 Porto, Portugal
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Anne Chauchereau
Cancers 2022, 14(8), 2001; https://doi.org/10.3390/cancers14082001
Received: 22 February 2022 / Revised: 12 April 2022 / Accepted: 13 April 2022 / Published: 15 April 2022
(This article belongs to the Topic Prostate Cancer: Symptoms, Diagnosis & Treatment)
Prostate cancer (PCa) is one of the most common cancers. Due to the limited and invasive approaches for PCa diagnosis, it is crucial to identify more accurate and non-invasive biomarkers for its detection. The aim of our study was to non-invasively uncover new protein targets for detecting PCa using a proteomics and proteogenomics approach. This work identified several dysregulated mutant protein isoforms in urine from PCa patients, some of them predicted to have a protective or an adverse role in these patients. These results are promising given urine’s non-invasive nature and offers an auspicious opportunity for research and development of PCa biomarkers.
To identify new protein targets for PCa detection, first, a shotgun discovery experiment was performed to characterize the urinary proteome of PCa patients. This revealed 18 differentially abundant urinary proteins in PCa patients. Second, selected targets were clinically tested by immunoblot, and the soluble E-cadherin fragment was detected for the first time in the urine of PCa patients. Third, the proteogenome landscape of these PCa patients was characterized, revealing 1665 mutant protein isoforms. Statistical analysis revealed 6 differentially abundant mutant protein isoforms in PCa patients. Analysis of the likely effects of mutations on protein function and PPIs involving the dysregulated mutant protein isoforms suggests a protective role of mutations HSPG2*Q1062H and VASN*R161Q and an adverse role of AMBP*A286G and CD55*S162L in PCa patients. This work originally characterized the urinary proteome, focusing on the proteogenome profile of PCa patients, which is usually overlooked in the analysis of PCa and body fluids. Combined analysis of mass spectrometry data using two different software packages was performed for the first time in the context of PCa, which increased the robustness of the data analysis. The application of proteogenomics to urine proteomic analysis can be very enriching in mutation-related diseases such as cancer. View Full-Text
Keywords: prostate cancer; urine; human; biomarker; proteome; proteogenome; label-free quantitation; immunoblot prostate cancer; urine; human; biomarker; proteome; proteogenome; label-free quantitation; immunoblot
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MDPI and ACS Style

Lima, T.; Barros, A.S.; Trindade, F.; Ferreira, R.; Leite-Moreira, A.; Barros-Silva, D.; Jerónimo, C.; Araújo, L.; Henrique, R.; Vitorino, R.; Fardilha, M. Application of Proteogenomics to Urine Analysis towards the Identification of Novel Biomarkers of Prostate Cancer: An Exploratory Study. Cancers 2022, 14, 2001. https://doi.org/10.3390/cancers14082001

AMA Style

Lima T, Barros AS, Trindade F, Ferreira R, Leite-Moreira A, Barros-Silva D, Jerónimo C, Araújo L, Henrique R, Vitorino R, Fardilha M. Application of Proteogenomics to Urine Analysis towards the Identification of Novel Biomarkers of Prostate Cancer: An Exploratory Study. Cancers. 2022; 14(8):2001. https://doi.org/10.3390/cancers14082001

Chicago/Turabian Style

Lima, Tânia, António S. Barros, Fábio Trindade, Rita Ferreira, Adelino Leite-Moreira, Daniela Barros-Silva, Carmen Jerónimo, Luís Araújo, Rui Henrique, Rui Vitorino, and Margarida Fardilha. 2022. "Application of Proteogenomics to Urine Analysis towards the Identification of Novel Biomarkers of Prostate Cancer: An Exploratory Study" Cancers 14, no. 8: 2001. https://doi.org/10.3390/cancers14082001

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