Comparative proteomics analysis in different stages of urothelial bladder cancer for identification of potential biomarkers: highlighted role for antioxidant activity

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Abstract

Background

Non-muscle-invasive bladder cancer (NMIBC) has a high recurrence rate and muscle-invasive bladder cancer (MIBC) has unfavorable outcomes in urothelial bladder cancer (UBC) patients. Complex UBC-related protein biomarkers for outcome prediction may provide a more efficient management approach with an improved clinical outcome. The aim of this study is to recognize tumor-associated proteins, which are differentially expressed in different stages of UBC patients compared non-cancerous tissues.

Methods

The proteome of tissue samples of 42 UBC patients (NMIBC n = 25 and MIBC n = 17) was subjected to two-dimensional electrophoresis (2-DE) combined with Liquid chromatography–mass spectrometry (LC–MS) system to identify differentially expressed proteins. The intensity of protein spots was quantified and compared with Prodigy SameSpots software. Functional, pathway, and interaction analyses of identified proteins were performed using geneontology (GO), PANTHER, Reactome, Gene MANIA, and STRING databases.

Results

Twelve proteins identified by LC-MS showed differential expression (over 1.5-fold, p < 0.05) by LC-MS, including 9 up-regulated in NMIBC and 3 up-regulated in MIBC patients. Proteins involved in the detoxification of reactive oxygen species and cellular responses to oxidative stress showed the most significant changes in UBC patients. Additionally, the most potential functions related to these detected proteins were associated with peroxidase, oxidoreductase, and antioxidant activity.

Conclusion

We identified several alterations in protein expression involved in canonical pathways which were correlated with the clinical outcomes suggested might be useful as promising biomarkers for early detection, monitoring, and prognosis of UBC.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12014-023-09419-8.

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Most cited references 67

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The mutational constraint spectrum quantified from variation in 141,456 humans

Konrad J. Karczewski, Laurent C. Francioli, Grace Tiao … (2021)

Genetic variants that inactivate protein-coding genes are a powerful source of information about the phenotypic consequences of gene disruption: genes that are crucial for the function of an organism will be depleted of such variants in natural populations, whereas non-essential genes will tolerate their accumulation. However, predicted loss-of-function variants are enriched for annotation errors, and tend to be found at extremely low frequencies, so their analysis requires careful variant annotation and very large sample sizes 1 . Here we describe the aggregation of 125,748 exomes and 15,708 genomes from human sequencing studies into the Genome Aggregation Database (gnomAD). We identify 443,769 high-confidence predicted loss-of-function variants in this cohort after filtering for artefacts caused by sequencing and annotation errors. Using an improved model of human mutation rates, we classify human protein-coding genes along a spectrum that represents tolerance to inactivation, validate this classification using data from model organisms and engineered human cells, and show that it can be used to improve the power of gene discovery for both common and rare diseases.

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Relationships among smoking, oxidative stress, inflammation, macromolecular damage, and cancer.

Andrew Caliri, Stella Tommasi, Ahmad Besaratinia (2021)

Smoking is a major risk factor for a variety of diseases, including cancer and immune-mediated inflammatory diseases. Tobacco smoke contains a mixture of chemicals, including a host of reactive oxygen- and nitrogen species (ROS and RNS), among others, that can damage cellular and sub-cellular targets, such as lipids, proteins, and nucleic acids. A growing body of evidence supports a key role for smoking-induced ROS and the resulting oxidative stress in inflammation and carcinogenesis. This comprehensive and up-to-date review covers four interrelated topics, including 'smoking', 'oxidative stress', 'inflammation', and 'cancer'. The review discusses each of the four topics, while exploring the intersections among the topics by highlighting the macromolecular damage attributable to ROS. Specifically, oxidative damage to macromolecular targets, such as lipid peroxidation, post-translational modification of proteins, and DNA adduction, as well as enzymatic and non-enzymatic antioxidant defense mechanisms, and the multi-faceted repair pathways of oxidized lesions are described. Also discussed are the biological consequences of oxidative damage to macromolecules if they evade the defense mechanisms and/or are not repaired properly or in time. Emphasis is placed on the genetic- and epigenetic alterations that may lead to transcriptional deregulation of functionally-important genes and disruption of regulatory elements. Smoking-associated oxidative stress also activates the inflammatory response pathway, which triggers a cascade of events of which ROS production is an initial yet indispensable step. The release of ROS at the site of damage and inflammation helps combat foreign pathogens and restores the injured tissue, while simultaneously increasing the burden of oxidative stress. This creates a vicious cycle in which smoking-related oxidative stress causes inflammation, which in turn, results in further generation of ROS, and potentially increased oxidative damage to macromolecular targets that may lead to cancer initiation and/or progression.

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The role of peroxiredoxins in cancer

Arianna Nicolussi, Sonia D'Inzeo, Carlo Capalbo … (2017)

Peroxiredoxins (PRDXs) are a ubiquitously expressed family of small (22–27 kDa) non-seleno peroxidases that catalyze the peroxide reduction of H2O2, organic hydroperoxides and peroxynitrite. They are highly involved in the control of various physiological functions, including cell growth, differentiation, apoptosis, embryonic development, lipid metabolism, the immune response, as well as cellular homeostasis. Although the protective role of PRDXs in cardiovascular and neurological diseases is well established, their role in cancer remains controversial. Increasing evidence suggests the involvement of PRDXs in carcinogenesis and in the development of drug resistance. Numerous types of cancer cells, in fact, are characterized by an increase in reactive oxygen species (ROS) production, and often exhibit an altered redox environment compared with normal cells. The present review focuses on the complex association between oxidant balance and cancer, and it provides a brief account of the involvement of PRDXs in tumorigenesis and in the development of chemoresistance.

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Author and article information

Contributors

Abbas Ghaderi:

ORCID: http://orcid.org/0000-0003-0849-3375

Ghaderia@sums.ac.ir

Journal

Journal ID (nlm-ta): Clin Proteomics

Journal ID (iso-abbrev): Clin Proteomics

Title: Clinical Proteomics

Publisher: BioMed Central (London )

ISSN (Print): 1542-6416

ISSN (Electronic): 1559-0275

Publication date (Electronic): 27 July 2023

Publication date PMC-release: 27 July 2023

Publication date Collection: 2023

Volume: 20

Electronic Location Identifier: 28

Affiliations

[1 ]GRID grid.412571.4, ISNI 0000 0000 8819 4698, Department of Immunology, School of Medicine, , Shiraz University of Medical Sciences, ; Shiraz, Iran

[2 ]GRID grid.412571.4, ISNI 0000 0000 8819 4698, Shiraz Institute for Cancer Research, School of Medicine, , Shiraz University of Medical Sciences, ; Shiraz, Iran

[3 ]GRID grid.412571.4, ISNI 0000 0000 8819 4698, Department of Urology, School of Medicine, , Shiraz University of Medical Sciences, ; Shiraz, Iran

[4 ]GRID grid.417689.5, Integrative Oncology Department, Breast Cancer Research Center, , Motamed Cancer Institute, ACECR, ; Tehran, Iran

[5 ]GRID grid.5117.2, ISNI 0000 0001 0742 471X, Department of Health Science and Technology, , Aalborg University, ; Gistrup, 9260 Denmark

[6 ]GRID grid.27530.33, ISNI 0000 0004 0646 7349, Clinical Cancer Research Center, , Aalborg University hospital, ; Gistrup, 9260 Denmark

Author information

Abbas Ghaderi http://orcid.org/0000-0003-0849-3375

Article

Publisher ID: 9419

DOI: 10.1186/s12014-023-09419-8

PMC ID: 10373361

PubMed ID: 37501157

SO-VID: 8091a22c-3f06-4466-960d-eb86613e0251

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 12 February 2023

Date accepted : 10 July 2023

Funding

Funded by: Danish National Mass Spectrometry Platform for Functional Proteomics

Award ID: 5072-00007B

Funded by: FundRef http://dx.doi.org/10.13039/501100004320, Shiraz University of Medical Sciences;

Award ID: 23083

Funded by: Shiraz Institute for Cancer research

Award ID: ICR-100-503

Custom metadata

ScienceOpen disciplines: Molecular medicine

Keywords: urothelial bladder cancer,proteomics,biomarker,cellular responses

Data availability:

ScienceOpen disciplines: Molecular medicine

Keywords: urothelial bladder cancer, proteomics, biomarker, cellular responses

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Comparative proteomics analysis in different stages of urothelial bladder cancer for identification of potential biomarkers: highlighted role for antioxidant activity

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Abstract

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Supplementary Information

Related collections

Bacterial extracellular vesicles

Most cited references 67

The mutational constraint spectrum quantified from variation in 141,456 humans

Relationships among smoking, oxidative stress, inflammation, macromolecular damage, and cancer.

The role of peroxiredoxins in cancer

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