Generic placeholder image

Protein & Peptide Letters

Editor-in-Chief

ISSN (Print): 0929-8665
ISSN (Online): 1875-5305

Research Article

Serum HSP90-Alpha and Oral Squamous Cell Carcinoma: A Prospective Biomarker

Author(s): Muhammad Usman, Amber Ilyas, Basir Syed, Zehra Hashim, Aftab Ahmed and Shamshad Zarina*

Volume 28, Issue 10, 2021

Published on: 16 June, 2021

Page: [1157 - 1163] Pages: 7

DOI: 10.2174/0929866528666210616112539

Price: $65

Abstract

Aim: This study aims to perform differential protein expression analysis of serum samples from Oral Squamous Cell Carcinoma (OSCC) patients and healthy controls in search of potential diagnostic and/or prognostic biomarker(s).

Objective: OSCC is usually diagnosed late, which results in poor survival and high mortality. Identification of non-invasive prognostic biomarkers is of utmost importance for early diagnosis and proper management of the disease; hence we used a proteomic approach to identify potential biomarkers from serum.

Methods: Serum samples (OSCC n=45 and control n=30) were depleted, and proteins were separated using 2-D gel electrophoresis followed by identification by mass spectrometric analysis. Gene expression analysis of identified proteins in malignant and normal tissue was also performed to complement proteomics studies.

Results: Among differentially expressed proteins, up-regulation of heat shock protein alpha (HSP90α) from the serum of oral cancer patients was observed. We also observed elevated levels of Haptoglobin (HP) along with downregulation of Type II keratin cytoskeletal 1(KRT1) and serum albumin (ALB) in oral cancer patients. Gene expression studies on identified proteins in malignant and normal tissue revealed a similar pattern with the exception of KRT1. We believe that elevated levels of serum HSP90 alpha might be used as a potential biomarker.

Conclusion: Our findings suggest a contribution of HSP90 alpha and other identified proteins in oral pathology as pro/anti-apoptotic modulators, thus considering their potential as predictive biomarkers.

Keywords: Serum biomarkers, OSCC, HSP90alpha, KRT1, haptoglobin, proteomics.

Graphical Abstract
[1]
Leemans, C.R.; Braakhuis, B.J.; Brakenhoff, R.H. The molecular biology of head and neck cancer. Nat. Rev. Cancer, 2011, 11(1), 9-22.
[http://dx.doi.org/10.1038/nrc2982] [PMID: 21160525]
[2]
Arantes, L.M.R.B.; de Carvalho, A.C.; Melendez, M.E.; Carvalho, A.L.; Goloni-Bertollo, E.M. Methylation as a biomarker for head and neck cancer. Oral Oncol., 2014, 50(6), 587-592.
[http://dx.doi.org/10.1016/j.oraloncology.2014.02.015] [PMID: 24656975]
[3]
Tanaka, T.; Tanaka, M.; Tanaka, T. Oral carcinogenesis and oral cancer chemoprevention: A review. Pathol. Res. Int., 2011, 2011, 431246-431246.
[http://dx.doi.org/10.4061/2011/431246] [PMID: 21660266]
[4]
Johnson, N. Tobacco use and oral cancer: A global perspective. J. Dent. Educ., 2001, 65(4), 328-339.
[http://dx.doi.org/10.1002/j.0022-0337.2001.65.4.tb03403.x] [PMID: 11336118]
[5]
Khan, Z.; Tönnies, J.; Müller, S. Smokeless tobacco and oral cancer in South Asia: A systematic review with meta-analysis. J. Cancer Epidemiol., 2014, 2014, 394696-394696.
[http://dx.doi.org/10.1155/2014/394696] [PMID: 25097551]
[6]
Bray, F.; Ferlay, J.; Soerjomataram, I.; Siegel, R.L.; Torre, L.A.; Jemal, A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2018, 68(6), 394-424.
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[7]
Ali, N.S.; Khuwaja, A.K.; Ali, T.; Hameed, R. Smokeless tobacco use among adult patients who visited family practice clinics in Karachi, Pakistan. J. Oral Pathol. Med., 2009, 38(5), 416-421.
[http://dx.doi.org/10.1111/j.1600-0714.2009.00754.x] [PMID: 19434816]
[8]
Sciubba, J. Oral Cancer: The importance of early diagnosis and treatment. 2001, 2(4), 239-254.
[9]
Gigliotti, J.; Madathil, S.; Makhoul, N. Delays in oral cavity cancer. Int. J. Oral Maxillofac. Surg., 2019, 48(9), 1131-1137.
[http://dx.doi.org/10.1016/j.ijom.2019.02.015] [PMID: 30878273]
[10]
Geyer, P.E.; Holdt, L.M.; Teupser, D.; Mann, M. Revisiting biomarker discovery by plasma proteomics. Mol. Syst. Biol., 2017, 13(9), 942-942.
[http://dx.doi.org/10.15252/msb.20156297] [PMID: 28951502]
[11]
Perera, F.P.; Weinstein, I.B. Molecular epidemiology: recent advances and future directions. Carcinogenesis, 2000, 21(3), 517-524.
[http://dx.doi.org/10.1093/carcin/21.3.517] [PMID: 10688872]
[12]
Zamay, T.N.; Zamay, G.S.; Kolovskaya, O.S.; Zukov, R.A.; Petrova, M.M.; Gargaun, A.; Berezovski, M.V.; Kichkailo, A.S. Current and prospective protein biomarkers of lung cancer. Cancers (Basel), 2017, 9(11), 155.
[http://dx.doi.org/10.3390/cancers9110155] [PMID: 29137182]
[13]
Barbosa, E.B. Proteomics: Methodologies and applications to the study of human diseases. Rev Assoc Med Bras, 2012, 58(3), 366-375.
[14]
Turhani, D.; Krapfenbauer, K.; Thurnher, D.; Langen, H.; Fountoulakis, M. Identification of differentially expressed, tumor-associated proteins in oral squamous cell carcinoma by proteomic analysis. Electrophoresis, 2006, 27(7), 1417-1423.
[http://dx.doi.org/10.1002/elps.200500510] [PMID: 16568407]
[15]
Malik, U.U.; Zarina, S.; Pennington, S.R. Oral squamous cell carcinoma: Key clinical questions, biomarker discovery, and the role of proteomics. Arch. Oral Biol., 2016, 63, 53-65.
[http://dx.doi.org/10.1016/j.archoralbio.2015.11.017] [PMID: 26691574]
[16]
Blatt, S.; Krüger, M.; Ziebart, T.; Sagheb, K.; Schiegnitz, E.; Goetze, E.; Al-Nawas, B.; Pabst, A.M. Biomarkers in diagnosis and therapy of oral squamous cell carcinoma: A review of the literature. J. Craniomaxillofac. Surg., 2017, 45(5), 722-730.
[http://dx.doi.org/10.1016/j.jcms.2017.01.033] [PMID: 28318929]
[17]
Malik, U.U.; Siddiqui, I.A.; Ilyas, A.; Hashim, Z.; Staunton, L.J.; Kwasnik, A.; Pennington, S.R.; Zarina, S. Identification of differentially expressed proteins from smokeless tobacco addicted patients suffering from oral squamous cell carcinoma. Pathol. Oncol. Res., 2020, 26(3), 1489-1497.
[18]
Beretta, L. Proteomics from the clinical perspective: Many hopes and much debate. Nat. Methods, 2007, 4(10), 785-786.
[http://dx.doi.org/10.1038/nmeth1007-785] [PMID: 17901867]
[19]
Fernández-Olavarría, A.; Mosquera-Pérez, R.; Díaz-Sánchez, R.M.; Serrera-Figallo, M.A.; Gutiérrez-Pérez, J.L.; Torres-Lagares, D. The role of serum biomarkers in the diagnosis and prognosis of oral cancer: A systematic review. J. Clin. Exp. Dent., 2016, 8(2), e184-e193.
[http://dx.doi.org/10.4317/jced.52736] [PMID: 27034760]
[20]
Rifai, N.; Gillette, M.A.; Carr, S.A. Protein biomarker discovery and validation: The long and uncertain path to clinical utility. Nat. Biotechnol., 2006, 24(8), 971-983.
[http://dx.doi.org/10.1038/nbt1235] [PMID: 16900146]
[21]
Hsiao, Y.C.; Chi, L.M.; Chien, K.Y.; Chiang, W.F.; Chen, S.F.; Chuang, Y.N.; Lin, S.Y.; Wu, C.C.; Chang, Y.T.; Chu, L.J.; Chen, Y.T.; Chia, S.L.; Chien, C.Y.; Chang, K.P.; Chang, Y.S.; Yu, J.S. Development of a multiplexed assay for oral cancer candidate biomarkers using peptide i mMunoaffinity enrichment and targeted mass spectrometry. Mol. Cell. Proteomics, 2017, 16(10), 1829-1849.
[http://dx.doi.org/10.1074/mcp.RA117.000147] [PMID: 28821604]
[22]
Zaidi, D.K. Protein expression profile of oral premalignant lesions. Int. J. Cell sci. & Molecular Biology, 2018, 5(1), 4-9.
[http://dx.doi.org/10.19080/IJCSMB.2018.05.555652]
[23]
Deschler, D. Neck dissection classification and tnm staging of head and neck cancer. 1991.
[24]
Ilyas, A.; Hashim, Z.; Zarina, S. Effects of 5′-azacytidine and alendronate on a hepatocellular carcinoma cell line: A proteomics perspective. Mol. Cell. Biochem., 2015, 405(1-2), 53-61.
[http://dx.doi.org/10.1007/s11010-015-2395-1] [PMID: 25854900]
[25]
Kirwan, A.; Utratna, M.; O’Dwyer, M.E.; Joshi, L.; Kilcoyne, M. Glycosylation-based serum biomarkers for cancer diagnostics and prognostics. BioMed Res. Int., 2015, 2015, 490531.
[http://dx.doi.org/10.1155/2015/490531] [PMID: 26509158]
[26]
Gao, J.; Garulacan, L.A.; Storm, S.M.; Opiteck, G.J.; Dubaquie, Y.; Hefta, S.A.; Dambach, D.M.; Dongre, A.R. Biomarker discovery in biological fluids. Methods, 2005, 35(3), 291-302.
[http://dx.doi.org/10.1016/j.ymeth.2004.08.020] [PMID: 15722225]
[27]
Lindquist, S.; Craig, E.A. The heat-shock proteins. Annu. Rev. Genet., 1988, 22, 631-677.
[http://dx.doi.org/10.1146/annurev.ge.22.120188.003215] [PMID: 2853609]
[28]
Li, Z.; Srivastava, P. Heat-shock proteins. Curr Protoc Immunol, 2004, 58(1), A-1T.
[29]
Wu, J.; Liu, T.; Rios, Z.; Mei, Q.; Lin, X.; Cao, S. Heat shock proteins and cancer. Trends Pharmacol. Sci., 2017, 38(3), 226-256.
[http://dx.doi.org/10.1016/j.tips.2016.11.009] [PMID: 28012700]
[30]
Fujita, N. Involvement of hsp90 in signaling and stability of 3-phosphoinositide-dependent kinase-1. 2002, 277, 10346-10353.
[31]
Deb, T.B.; Zuo, A.H.; Wang, Y.; Barndt, R.J.; Cheema, A.K.; Sengupta, S.; Coticchia, C.M.; Johnson, M.D. Pnck induces ligand-independent EGFR degradation by probable perturbation of the Hsp90 chaperone complex. Am. J. Physiol. Cell Physiol., 2011, 300(5), C1139-C1154.
[http://dx.doi.org/10.1152/ajpcell.00167.2010] [PMID: 21325639]
[32]
Wang, X.; Song, X.; Zhuo, W.; Fu, Y.; Shi, H.; Liang, Y.; Tong, M.; Chang, G.; Luo, Y. The regulatory mechanism of Hsp90alpha secretion and its function in tumor malignancy. Proc. Natl. Acad. Sci. USA, 2009, 106(50), 21288-21293.
[http://dx.doi.org/10.1073/pnas.0908151106] [PMID: 19965370]
[33]
Shi, Y.; Liu, X.; Lou, J.; Han, X.; Zhang, L.; Wang, Q.; Li, B.; Dong, M.; Zhang, Y. Plasma levels of heat shock protein 90 alpha associated with lung cancer development and treatment responses. Clin. Cancer Res., 2014, 20(23), 6016-6022.
[http://dx.doi.org/10.1158/1078-0432.CCR-14-0174] [PMID: 25316816]
[34]
Chang, W.C.; Tsai, P.T.; Lin, C.K.; Shieh, Y.S.; Chen, Y.W. Expression pattern of heat shock protein 90 in patients with oral squamous cell carcinoma in northern Taiwan. Br. J. Oral Maxillofac. Surg., 2017, 55(3), 281-286.
[http://dx.doi.org/10.1016/j.bjoms.2017.01.008] [PMID: 28209383]
[35]
Moser, C.; Lang, S.A.; Stoeltzing, O. Heat-shock protein 90 (Hsp90) as a molecular target for therapy of gastrointestinal cancer. Anticancer Res., 2009, 29(6), 2031-2042.
[PMID: 19528462]
[36]
Barrott, J.J.; Haystead, T.A. Hsp90, an unlikely ally in the war on cancer. FEBS J., 2013, 280(6), 1381-1396.
[http://dx.doi.org/10.1111/febs.12147] [PMID: 23356585]
[37]
Liu, H.; Lu, J.; Hua, Y.; Zhang, P.; Liang, Z.; Ruan, L.; Lian, C.; Shi, H.; Chen, K.; Tu, Z. Targeting heat-shock protein 90 with ganetespib for molecularly targeted therapy of gastric cancer. Cell Death Dis., 2015, 6, e1595.
[http://dx.doi.org/10.1038/cddis.2014.555] [PMID: 25590805]
[38]
Usman, M. Tanveer, F.; Ilyas, A.; Zarina, S. Varlitinib mediates its activity through down regulating mapk/egfr pathway in oral cancer. Curr. Proteom., 2019, 17(1), 51-58.
[39]
Sadrzadeh, S.M.; Bozorgmehr, J. Haptoglobin phenotypes in health and disorders. Am. J. Clin. Pathol., 2004, 121(Suppl.), S97-S104.
[PMID: 15298155]
[40]
Tan, Y.; Ma, S.Y.; Wang, F.Q.; Meng, H.P.; Mei, C.; Liu, A.; Wu, H.R. Proteomic-based analysis for identification of potential serum biomarkers in gallbladder cancer. Oncol. Rep., 2011, 26(4), 853-859.
[PMID: 21687958]
[41]
Mandato, V.D.; Magnani, E.; Abrate, M.; Casali, B.; Nicoli, D.; Farnetti, E.; Formisano, D.; Pirillo, D.; Ciarlini, G.; De Iaco, P.; Strada, I.; Zamagni, C.; La Sala, G.B. Haptoglobin phenotype and epithelial ovarian cancer. Anticancer Res., 2012, 32(10), 4353-4358.
[PMID: 23060558]
[42]
Hamrita, B.; Chahed, K.; Trimeche, M.; Guillier, C.L.; Ha mMann, P.; Chaïeb, A.; Korbi, S.; Chouchane, L. Proteomics-based identification of alpha1-antitrypsin and haptoglobin precursors as novel serum markers in infiltrating ductal breast carcinomas. Clin. Chim. Acta, 2009, 404(2), 111-118.
[http://dx.doi.org/10.1016/j.cca.2009.03.033] [PMID: 19306859]
[43]
Park, J.; Yang, J.S.; Jung, G.; Woo, H.I.; Park, H.D.; Kim, J.W.; Huh, W.; Ko, J.W.; Kim, H.; Cho, J.Y.; Lee, S.Y. Subunit-specific mass spectrometry method identifies haptoglobin subunit alpha as a diagnostic marker in non-small cell lung cancer. J. Proteomics, 2013, 94, 302-310.
[http://dx.doi.org/10.1016/j.jprot.2013.09.019] [PMID: 24120528]
[44]
Lai, C.H.; Chang, N.W.; Lin, C.F.; Lin, C.D.; Lin, Y.J.; Wan, L.; Sheu, J.J.; Chen, S.Y.; Huang, Y.P.; Sing, Y.T.; Tao, T.W.; Lai, C.K.; Tsai, M.H.; Chan, H.L.; Jou, Y.J.; Lin, C.W. Proteomics-based identification of haptoglobin as a novel plasma biomarker in oral squamous cell carcinoma. Clin. Chim. Acta, 2010, 411(13-14), 984-991.
[http://dx.doi.org/10.1016/j.cca.2010.03.028] [PMID: 20359475]
[45]
Chang, S-C.; Lin, W.L.; Chang, Y.F.; Lee, C.T.; Wu, J.S.; Hsu, P.H.; Chang, C.F. Glycoproteomic identification of novel plasma biomarkers for oral cancer. Yao Wu Shi Pin Fen Xi, 2019, 27(2), 483-493.
[http://dx.doi.org/10.1016/j.jfda.2018.12.008] [PMID: 30987719]
[46]
Wang, Z.; Jiang, L.; Huang, C.; Li, Z.; Chen, L.; Gou, L.; Chen, P.; Tong, A.; Tang, M.; Gao, F.; Shen, J.; Zhang, Y.; Bai, J.; Zhou, M.; Miao, D.; Chen, Q. Comparative proteomics approach to screening of potential diagnostic and therapeutic targets for oral squamous cell carcinoma. Mol. Cell. Proteomics, 2008, 7(9), 1639-1650.
[http://dx.doi.org/10.1074/mcp.M700520-MCP200] [PMID: 18458027]
[47]
Lee, C.C.; Ho, H.C.; Chien, S.H.; Hsiao, S.H.; Hung, S.K.; Huang, T.T.; Yu, C.C.; Chang, S.M.; Huang, H.H.; Su, Y.C. Association of acute phase protein-haptoglobin, and epithelial-mesenchymal transition in buccal cancer: A preliminary report. Clin. Chem. Lab. Med., 2013, 51(2), 429-437.
[http://dx.doi.org/10.1515/cclm-2012-0197] [PMID: 23093274]
[48]
Garibay-Cerdenares, O.L.; Hernández-Ramírez, V.I.; Osorio-Trujillo, J.C.; Gallardo-Rincón, D.; Talamás-Rohana, P. Haptoglobin and CCR2 receptor expression in ovarian cancer cells that were exposed to ascitic fluid: Exploring a new role of haptoglobin in the tumoral microenvironment. Cell Adhes. Migr., 2015, 9(5), 394-405.
[http://dx.doi.org/10.1080/19336918.2015.1035504] [PMID: 26211665]
[49]
Fanali, G.; di Masi, A.; Trezza, V.; Marino, M.; Fasano, M.; Ascenzi, P. Human serum albumin: From bench to bedside. Mol. Aspects Med., 2012, 33(3), 209-290.
[http://dx.doi.org/10.1016/j.mam.2011.12.002] [PMID: 22230555]
[50]
Metgud, R.; Patel, S. Serum and salivary levels of albumin as diagnostic tools for oral pre-malignancy and oral malignancy. Biotech. Histochem., 2014, 89(1), 8-13.
[http://dx.doi.org/10.3109/10520295.2013.793394] [PMID: 23738795]
[51]
Chandran, V. Protein oxidation: A potential cause of hypoalbuminemia in oral cancer. Biomed. Res., 2012, 23, 227-230.
[52]
Frei, E. Albumin binding ligands and albumin conjugate uptake by cancer cells. Diabetol. Metab. Syndr., 2011, 3(1), 11-11.
[http://dx.doi.org/10.1186/1758-5996-3-11] [PMID: 21676260]
[53]
Stehle, G.; Sinn, H.; Wunder, A.; Schrenk, H.H.; Stewart, J.C.; Hartung, G.; Maier-Borst, W.; Heene, D.L. Plasma protein (albumin) catabolism by the tumor itself--implications for tumor metabolism and the genesis of cachexia. Crit. Rev. Oncol. Hematol., 1997, 26(2), 77-100.
[http://dx.doi.org/10.1016/S1040-8428(97)00015-2] [PMID: 9298326]
[54]
Jones, D.T.; Ganeshaguru, K.; Anderson, R.J.; Jackson, T.R.; Bruckdorfer, K.R.; Low, S.Y.; Palmqvist, L.; Prentice, H.G.; Hoffbrand, A.V.; Mehta, A.B.; Wickremasinghe, R.G. Albumin activates the AKT signaling pathway and protects B-chronic lymphocytic leukemia cells from chlorambucil- and radiation-induced apoptosis. Blood, 2003, 101(8), 3174-3180.
[http://dx.doi.org/10.1182/blood-2002-07-2143] [PMID: 12480711]
[55]
Petrosyan, A.; Ali, M.F.; Cheng, P-W. Keratin 1 plays a critical role in golgi localization of core 2 N-acetylglucosaminyltransferase M via interaction with its cytoplasmic tail. J. Biol. Chem., 2015, 290(10), 6256-6269.
[http://dx.doi.org/10.1074/jbc.M114.618702] [PMID: 25605727]
[56]
Toivola, D.M.; Boor, P.; Alam, C.; Strnad, P. Keratins in health and disease. Curr. Opin. Cell Biol., 2015, 32, 73-81.
[http://dx.doi.org/10.1016/j.ceb.2014.12.008] [PMID: 25599598]
[57]
Kim, K.H.; Schwartz, F.; Fuchs, E. Differences in keratin synthesis between normal epithelial cells and squamous cell carcinomas are mediated by vitamin A. Proc. Natl. Acad. Sci. USA, 1984, 81(14), 4280-4284.
[http://dx.doi.org/10.1073/pnas.81.14.4280] [PMID: 6205393]
[58]
Roman, E.; Lunde, M.L.; Miron, T.; Warnakulasauriya, S.; Johannessen, A.C.; Vasstrand, E.N.; Ibrahim, S.O. Analysis of protein expression profile of oral squamous cell carcinoma by MALDI-TOF-MS. Anticancer Res., 2013, 33(3), 837-845.
[PMID: 23482752]
[59]
Ku, N-O.; Strnad, P.; Bantel, H.; Omary, M.B. Keratins: Biomarkers and modulators of apoptotic and necrotic cell death in the liver. Hepatology, 2016, 64(3), 966-976.
[http://dx.doi.org/10.1002/hep.28493] [PMID: 26853542]
[60]
Hsu, Y-P.; Hsieh, C.H.; Chien, H.T.; Lai, C.H.; Tsao, C.K.; Liao, C.T.; Kang, C.J.; Wang, H.M.; Chang, J.T.; Huang, S.F. Serum markers of CYFRA 21-1 and C-reactive proteins in oral squamous cell carcinoma. World J. Surg. Oncol., 2015, 13, 253-253.
[http://dx.doi.org/10.1186/s12957-015-0656-9] [PMID: 26292957]
[61]
Khowal, S. Assessment of cellular and serum proteome from tongue squamous cell carcinoma patient lacking addictive proclivities for tobacco, betel nut, and alcohol: Case study. 2018, 119(7), 5186-5221.
[http://dx.doi.org/10.1002/jcb.26554]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy