Evaluation of Haptoglobin and Its Proteoforms as Glioblastoma Markers
Abstract
:1. Introduction
2. Results
2.1. Detection of Differentially Expressed Proteins in GBM Plasma Samples versus Non-Tumorous Plasma Samples Based on SDS-PAGE
2.2. An Analysis Based on Spots in 2DE Gels
2.3. A Sectional 2DE Analysis
3. Discussion
4. Materials and Methods
4.1. Cells and Plasma
4.2. Immunostaining (Western Blotting)
4.3. Sample Preparation and Two-Dimensional Electrophoresis (2DE)
4.4. ESI LC-MS/MS Analysis
4.5. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
MS | Mass spectrometry |
ESI LC-MS/MS | Liquid chromatography-electrospray ionization-tandem mass spectrometry |
GBM | The glioblastoma multiform |
2DE | Two-dimensional gel electrophoresis |
2D | Two-dimensional |
emPAI | An exponential modified form of protein abundance index |
References
- Furnari, F.B.; Fenton, T.; Bachoo, R.M.; Mukasa, A.; Stommel, J.M.; Stegh, A.; Hahn, W.C.; Ligon, K.L.; Louis, D.N.; Brennan, C.; et al. Malignant astrocytic glioma: Genetics, biology, and paths to treatment. Genes Dev. 2007, 21, 2683–2710. [Google Scholar] [CrossRef] [Green Version]
- Louis, D.N.; Ohgaki, H.; Wiestler, O.D.; Cavenee, W.K.; Burger, P.C.; Jouvet, A.; Scheithauer, B.W.; Kleihues, P. The 2007 WHO classification of tumours of the central nervous system. Acta Neuropathol. 2007, 114, 97–109. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Stupp, R.; Mason, W.P.; Van Den Bent, M.J.; Weller, M.; Fisher, B.; Taphoorn, M.J.; Belanger, K.; Brandes, A.A.; Marosi, C.; Bogdahn, U.; et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N. Engl. J. Med. 2005, 352, 987–996. [Google Scholar] [CrossRef]
- Szopa, W.; Burley, T.A.; Kramer-Marek, G.; Kaspera, W. Diagnostic and Therapeutic Biomarkers in Glioblastoma: Current Status and Future Perspectives. Biomed. Res. Int. 2017, 2017, 8013575. [Google Scholar] [CrossRef] [Green Version]
- Alix-Panabieres, C.P. Challenges in circulating tumour cell research. Nat. Rev. Cancer 2014, 14, 523–631. [Google Scholar] [CrossRef]
- Miller, A.M.; Shah, R.H.; Pentsova, E.I.; Pourmaleki, M.; Briggs, S.; Distefano, N.; Zheng, Y.; Skakodub, A.; Mehta, S.A.; Campos, C.; et al. Tracking tumour evolution in glioma through liquid biopsies of cerebrospinal fluid. Nature 2019, 565, 654–658. [Google Scholar] [CrossRef] [PubMed]
- Müller Bark, J.; Kulasinghe, A.; Chua, B.; Day, B.W.; Punyadeera, C. Circulating biomarkers in patients with glioblastoma. Br. J. Cancer 2020, 122, 295–305. [Google Scholar] [CrossRef] [Green Version]
- Chen, Z.; Hambardzumyan, D. Immune microenvironment in glioblastoma subtypes. Front. Immunol. 2018, 9, 1004. [Google Scholar] [CrossRef] [Green Version]
- Allard, W.J.; Matera, J.; Miller, M.C.; Repollet, M.; Connelly, M.C.; Rao, C.; Tibbe, A.G.; Uhr, J.W.; Terstappen, L.W. Tumor cells circulate in the peripheral blood of all major carcinomas but not in healthy subjects or patients with nonmalignant diseases. Clin. Cancer Res. 2004, 10, 6897–6904. [Google Scholar] [CrossRef] [Green Version]
- Zhang, R.; Tremblay, T.L.; McDermid, A.; Thibault, P.; Stanimirovic, D. Identification of differentially expressed proteins in human glioblastoma cell lines and tumors. Glia 2003, 42, 194–208. [Google Scholar] [CrossRef] [PubMed]
- Cohen, A.L.; Colman, H. Glioma biology and molecular markers. Cancer Treat. Res. 2015, 163, 15–30. [Google Scholar] [PubMed]
- Naryzhny, S.N.; Ronzhina, N.L.; Mainskova, M.A.; Belyakova, N.V.; Pantina, R.A.; Filatov, M.V. Development of barcode and proteome profiling of glioblastoma. Biochem. Suppl. Ser. B Biomed. Chem. 2014, 8, 243–251. [Google Scholar]
- Petrenko, E.S.; Kopylov, A.T.; Kleist, O.A.; Legina, O.K.; Belyakova, N.; Pantina, R.; Naryzhny, S. Searching for Specific Markers of Glioblastoma: Analysis of Glioblastoma Cell Proteoforms. Cell Tissue Biol. 2018, 12, 455–459. [Google Scholar] [CrossRef]
- Naryzhny, S.N.; Maynskova, M.A.; Zgoda, V.G.; Ronzhina, N.L.; Novikova, S.E.; Belyakova, N.V.; Kleyst, O.A.; Legina, O.K.; Pantina, R.A.; Filatov, M. Proteomic Profiling of High-grade Glioblastoma Using Virtual-experimental 2DE. J. Proteom. Bioinform. 2016, 9, 158–165. [Google Scholar] [CrossRef] [Green Version]
- Naryzhny, S.; Volnitskiy, A.; Kopylov, A.; Zorina, E.; Kamyshinsky, R.; Bairamukov, V.; Garaeva, L.; Shlikht, A.; Shtam, T. Proteome of Glioblastoma-Derived Exosomes as a Source of Biomarkers. Biomedicines 2020, 8, 216. [Google Scholar] [CrossRef]
- Zhang, S.; Shang, S.; Li, W.; Qin, X.; Liu, Y. Insights on N-glycosylation of human haptoglobin and its association with cancers. Glycobiology 2016, 26, 684–692. [Google Scholar] [CrossRef] [PubMed]
- Kumar, D.M.; Thota, B.; Shinde, S.V.; Prasanna, K.V.; Hegde, A.S.; Arivazhagan, A.; Chandramouli, B.A.; Santosh, V.; Somasundaram, K. Proteomic identification of haptoglobin α2 as a glioblastoma serum biomarker: Implications in cancer cell migration and tumor growth. J. Proteome Res. 2010, 9, 5557–5567. [Google Scholar] [CrossRef] [PubMed]
- Gollapalli, K.; Ray, S.; Srivastava, R.; Renu, D.; Singh, P.; Dhali, S.; Bajpai Dikshit, J.; Srikanth, R.; Moiyadi, A.; Srivastava, S. Investigation of serum proteome alterations in human glioblastoma multiforme. Proteomics 2012, 12, 2378–2390. [Google Scholar] [CrossRef] [PubMed]
- Garibay-Cerdenares, O.L.; Hernández-Ramírez, V.I.; Osorio-Trujillo, J.C.; Hernández-Ortíz, M.; Gallardo-Rincón, D.; De León, D.C.; Encarnación-Guevara, S.; Villegas-Pineda, J.; Talamás-Rohana, P. Proteomic identification of fucosylated haptoglobin alpha isoforms in ascitic fluids and its localization in ovarian carcinoma tissues from Mexican patients. J. Ovarian Res. 2014, 7, 27. [Google Scholar] [CrossRef] [Green Version]
- Ye, B.; Cramer, D.W.; Skates, S.J.; Gygi, S.P.; Pratomo, V.; Fu, L.; Horick, N.K.; Licklider, L.J.; Schorge, J.O.; Berkowitz, R.S.; et al. Haptoglobin-α subunit as potential serum biomarker in ovarian cancer: Identification and characterization using proteomic profiling and mass spectrometry. Clin. Cancer Res. 2003, 9, 2904–2911. [Google Scholar]
- Naryzhny, S.N.; Legina, O.K. Haptoglobin as a biomarker. Biomed. Khimiya 2021, 67, 105–118. [Google Scholar] [CrossRef]
- Shih, A.W.Y.; Mcfarlane, A.; Verhovsek, M. Haptoglobin testing in hemolysis: Measurement and interpretation. Am. J. Hematol. 2014, 89, 443–447. [Google Scholar] [CrossRef] [PubMed]
- Clerc, F.; Reiding, K.R.; Jansen, B.C.; Kammeijer, G.S.; Bondt, A.; Wuhrer, M. Human plasma protein N-glycosylation. Glycoconj. J. 2016, 33, 309–343. [Google Scholar] [CrossRef] [Green Version]
- Pompach, P.; Brnakova, Z.; Sanda, M.; Wu, J.; Edwards, N.; Goldman, R. Site-specific glycoforms of haptoglobin in liver cirrhosis and hepatocellular carcinoma. Mol. Cell. Proteom. 2013, 12, 1281–1293. [Google Scholar] [CrossRef] [Green Version]
- Mikkat, S.; Koy, C.; Ulbrich, M.; Ringel, B.; Glocker, M.O. Mass spectrometric protein structure characterization reveals cause of migration differences of haptoglobin α chains in two-dimensional gel electrophoresis. Proteomics 2004, 4, 3921–3932. [Google Scholar] [CrossRef] [PubMed]
- Fasano, A. Zonulin and its regulation of intestinal barrier function: The biological door to inflammation, autoimmunity, and cancer. Physiol. Rev. 2011, 91, 151–175. [Google Scholar] [CrossRef] [Green Version]
- Tripathi, A.; Lammers, K.M.; Goldblum, S.; Shea-Donohue, T.; Netzel-Arnett, S.; Buzza, M.S.; Antalis, T.M.; Vogel, S.N.; Zhao, A.; Yang, S.; et al. Identification of human zonulin, a physiological modulator of tight junctions, as prehaptoglobin-2. Proc. Natl. Acad. Sci. USA 2009, 106, 16799–16804. [Google Scholar] [CrossRef] [Green Version]
- Ohlsson, B.; Orho-Melander, M.; Nelsson, P.M. Higher Levels of Serum Zonulin May Rather Be Associated with Increased Risk of Obesity and Hyperlipidemia, Than with Gastrointestinal Symptoms or Disease Manifestations. Int. J. Mol. Sci. 2017, 18, 582. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hoogland, C.; Mostaguir, K.; Sanchez, J.C.; Hochstrasser, D.F.; Appel, R.D. SWISS-2DPAGE, ten years later. Proteomics 2004, 4, 2352–2356. [Google Scholar] [CrossRef]
- Naryzhny, S.N.; Maynskova, M.A.; Zgoda, V.G.; Ronzhina, N.L.; Kleyst, O.A.; Vakhrushev, I.V.; Archakov, A.I. Virtual-Experimental 2DE Approach in Chromosome-Centric Human Proteome Project. J. Proteome Res. 2016, 15, 525–530. [Google Scholar] [CrossRef] [PubMed]
- Kopylov, A.T.; Ilgisonis, E.V.; Moysa, A.A.; Tikhonova, O.V.; Zavialova, M.G.; Novikova, S.E.; Lisitsa, A.V.; Ponomarenko, E.A.; Moshkovskii, S.A.; Markin, A.A.; et al. Targeted Quantitative Screening of Chromosome 18 Encoded Proteome in Plasma Samples of Astronaut Candidates. J. Proteome Res. 2016, 15, 4039–4046. [Google Scholar] [CrossRef] [PubMed]
- Skardelly, M.; Armbruster, F.P.; Meixensberger, J.; Hilbig, H. Expression of zonulin, c-kit, and glial fibrillary acidic protein in human gliomas. Transl. Oncol. 2009, 2, 117–120. [Google Scholar] [CrossRef] [Green Version]
- Oh, M.K.; Park, H.J.; Lee, J.H.; Bae, H.M.; Kim, I.S. Single chain precursor prohaptoglobin promotes angiogenesis by upregulating expression of vascular endothelial growth factor (VEGF) and VEGF receptor2. FEBS Lett. 2015, 589, 1009–1017. [Google Scholar] [CrossRef] [Green Version]
- Díaz-Coránguez, M.; Segovia, J.; López-Ornelas, A.; Puerta-Guardo, H.; Ludert, J.; Chávez, B.; Meraz-Cruz, N.; González-Mariscal, L. Transmigration of Neural Stem Cells across the Blood Brain Barrier Induced by Glioma Cells. PLoS ONE 2013, 8, e60655. [Google Scholar] [CrossRef] [Green Version]
- Petushkova, N.A.; Zgoda, V.G.; Pyatnitskiy, M.A.; Larina, O.V.; Teryaeva, N.B.; Potapov, A.A.; Lisitsa, A.V. Post-translational modifications of FDA-approved plasma biomarkers in glioblastoma samples. PLoS ONE 2017, 12, e0177427. [Google Scholar] [CrossRef] [PubMed]
- Naryzhny, S.N. Blue Dry Western: Simple, economic, informative, and fast way of immunodetection. Anal. Biochem. 2009, 392, 90–95. [Google Scholar] [CrossRef]
- Vaudel, M.; Barsnes, H.; Berven, F.S.; Sickmann, A.; Martens, L. SearchGUI: An open-source graphical user interface for simultaneous OMSSA and X!Tandem searches. Proteomics 2011, 11, 996–999. [Google Scholar] [CrossRef]
- Linhares, P.; Carvalho, B.; Vaz, R.; Costa, B.M. Glioblastoma: Is there any blood biomarker with true clinical relevance? Int. J. Mol. Sci. 2020, 21, 5809. [Google Scholar] [CrossRef] [PubMed]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Naryzhny, S.; Ronzhina, N.; Zorina, E.; Kabachenko, F.; Zavialova, M.; Zgoda, V.; Klopov, N.; Legina, O.; Pantina, R. Evaluation of Haptoglobin and Its Proteoforms as Glioblastoma Markers. Int. J. Mol. Sci. 2021, 22, 6533. https://doi.org/10.3390/ijms22126533
Naryzhny S, Ronzhina N, Zorina E, Kabachenko F, Zavialova M, Zgoda V, Klopov N, Legina O, Pantina R. Evaluation of Haptoglobin and Its Proteoforms as Glioblastoma Markers. International Journal of Molecular Sciences. 2021; 22(12):6533. https://doi.org/10.3390/ijms22126533
Chicago/Turabian StyleNaryzhny, Stanislav, Natalia Ronzhina, Elena Zorina, Fedor Kabachenko, Maria Zavialova, Viktor Zgoda, Nikolai Klopov, Olga Legina, and Rimma Pantina. 2021. "Evaluation of Haptoglobin and Its Proteoforms as Glioblastoma Markers" International Journal of Molecular Sciences 22, no. 12: 6533. https://doi.org/10.3390/ijms22126533