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Published in: Journal of Cancer Research and Clinical Oncology 3/2019

01-03-2019 | Oral Cancer | Original Article – Cancer Research

FTIR-based spectrum of salivary exosomes coupled with computational-aided discriminating analysis in the diagnosis of oral cancer

Authors: Ayelet Zlotogorski-Hurvitz, Ben Zion Dekel, Dov Malonek, Ran Yahalom, Marilena Vered

Published in: Journal of Cancer Research and Clinical Oncology | Issue 3/2019

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Abstract

Purpose

To determine the Fourier-transform infrared (FTIR) spectra of salivary exosomes from oral cancer (OC) patients and healthy individuals (HI) and to assess its diagnostic potential using computational-aided models.

Methods

Whole saliva samples were collected from 21 OC patients and 13 HI. Exosomes were pelleted using differential centrifugation (12,000g, 120,000g). The mid-infrared (IR) absorbance spectra (900–5000 cm− 1 range) were measured using MIR8025 Oriel Fourier-transform IR equipped with a PIKE MIRacle ZnSe attenuated total reflectance attachment. Machine learning techniques, utilized to build discrimination models for the absorbance data of OC and HI, included the principal component analysis–linear discriminant analysis (PCA–LDA) and support vector machine (SVM) classification. Sensitivity, specificity and the area under the receiver operating characteristic curve were calculated.

Results

IR spectra of OC were consistently different from HI at 1072 cm− 1 (nucleic acids), 2924 cm− 1 and 2854 cm− 1 (membranous lipids), and 1543 cm− 1 (transmembrane proteins). The PCA–LDA discrimination model correctly classified the samples with a sensitivity of 100%, specificity of 89% and accuracy of 95%, and the SVM showed a training accuracy of 100% and a cross-validation accuracy of 89%.

Conclusion

We showed the specific IR spectral signature for OC salivary exosomes, which was accurately differentiated from HI exosomes based on detecting subtle changes in the conformations of proteins, lipids and nucleic acids using optimized artificial neural networks with small data sets. This non-invasive method should be further investigated for diagnosis of oral cancer at its very early stages or in oral lesions with potential for malignant transformation.
Literature
go back to reference Baker MJ, Gazi E, Brown MD, Shanks JH, Gardner P, Clarke NW (2008) FTIR-based spectroscopic analysis in the identification of clinically aggressive prostate cancer. Br J Cancer 99:1859–1866CrossRefPubMedCentralPubMed Baker MJ, Gazi E, Brown MD, Shanks JH, Gardner P, Clarke NW (2008) FTIR-based spectroscopic analysis in the identification of clinically aggressive prostate cancer. Br J Cancer 99:1859–1866CrossRefPubMedCentralPubMed
go back to reference Christoua C, Agapioua A, Kokkinoftab R (2018) Use of FTIR spectroscopy and chemometrics for the classification of carobs origin. J Adv Res 10:1–8CrossRef Christoua C, Agapioua A, Kokkinoftab R (2018) Use of FTIR spectroscopy and chemometrics for the classification of carobs origin. J Adv Res 10:1–8CrossRef
go back to reference Dave N, Lorenz-Fonfria VA, Leblanc G, Padros E (2008) FTIR spectroscopy of secondary-structure reorientation of melibiose permease modulated by substrate binding. Biophys J 94:3659–3670CrossRefPubMed Dave N, Lorenz-Fonfria VA, Leblanc G, Padros E (2008) FTIR spectroscopy of secondary-structure reorientation of melibiose permease modulated by substrate binding. Biophys J 94:3659–3670CrossRefPubMed
go back to reference Dukor RK (2006) Vibrational spectroscopy in the detection of cancer. In: Griffiths P, Chalmers JM (eds) Handbook of vibrational spectroscopy. Wiley, Hoboken, pp 3335–3361 Dukor RK (2006) Vibrational spectroscopy in the detection of cancer. In: Griffiths P, Chalmers JM (eds) Handbook of vibrational spectroscopy. Wiley, Hoboken, pp 3335–3361
go back to reference Fantini J, Yahi N (2015) Lipid metabolism and oxidation in neurons and glial cells. In: Fantini J, Yahi N (eds) Brain lipids in synaptic function and neurological disease—clues to innovative therapeutic strategies for brain disorders. Elsevier, Amsterdam, pp 53–85CrossRef Fantini J, Yahi N (2015) Lipid metabolism and oxidation in neurons and glial cells. In: Fantini J, Yahi N (eds) Brain lipids in synaptic function and neurological disease—clues to innovative therapeutic strategies for brain disorders. Elsevier, Amsterdam, pp 53–85CrossRef
go back to reference Ferlay J, Soerjomataram II, Dikshit R, Eser S, Mathers C, Rebelo M et al (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136:E359–E386CrossRefPubMed Ferlay J, Soerjomataram II, Dikshit R, Eser S, Mathers C, Rebelo M et al (2015) Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136:E359–E386CrossRefPubMed
go back to reference Fushiki T (2011) Estimation of prediction error by using K-fold cross-validation. Stat Comput 21:137–146CrossRef Fushiki T (2011) Estimation of prediction error by using K-fold cross-validation. Stat Comput 21:137–146CrossRef
go back to reference Gao Y, Huo X, Dong L, Sun X, Sai H, Wei G et al (2015) Fourier transform infrared microspectroscopy monitoring of 5-fluorouracil-induced apoptosis in SW620 colon cancer cells. Mol Med Rep 11:2585–25891CrossRefPubMed Gao Y, Huo X, Dong L, Sun X, Sai H, Wei G et al (2015) Fourier transform infrared microspectroscopy monitoring of 5-fluorouracil-induced apoptosis in SW620 colon cancer cells. Mol Med Rep 11:2585–25891CrossRefPubMed
go back to reference Katsiougiannis S, Chia D, Kim Y, Singh RP, Wong DT (2017) Saliva exosomes from pancreatic tumor-bearing mice modulate NK cell phenotype and antitumor cytotoxicity. FASEB J 31:998–1010CrossRefPubMed Katsiougiannis S, Chia D, Kim Y, Singh RP, Wong DT (2017) Saliva exosomes from pancreatic tumor-bearing mice modulate NK cell phenotype and antitumor cytotoxicity. FASEB J 31:998–1010CrossRefPubMed
go back to reference Krafft C, Wilhem K, Eremin A, Nestel S, von Bubnoff N, Schultze-Seeman W et al (2017) A specific spectral signature of serum and plasma-derived extracellular vesicles for cancer screening. Nanomed NBM 13:835–841CrossRef Krafft C, Wilhem K, Eremin A, Nestel S, von Bubnoff N, Schultze-Seeman W et al (2017) A specific spectral signature of serum and plasma-derived extracellular vesicles for cancer screening. Nanomed NBM 13:835–841CrossRef
go back to reference Lau C, Kim Y, Chia D, Spielmann N, Eibl G, Elashoff D et al (2013) Role of pancreatic cancer-derived exosomes in salivary biomarker development. J Biol Chem 288:26888–26897CrossRefPubMedCentralPubMed Lau C, Kim Y, Chia D, Spielmann N, Eibl G, Elashoff D et al (2013) Role of pancreatic cancer-derived exosomes in salivary biomarker development. J Biol Chem 288:26888–26897CrossRefPubMedCentralPubMed
go back to reference Li Q, Hao C, Kang X, Zhang J, Sun X, Wang W et al (2017) Colorectal cancer and colitis diagnosis using Fourier transform infrared spectroscopy and an improved k-nearest-neighbor classifier. Sensors 17:2739CrossRef Li Q, Hao C, Kang X, Zhang J, Sun X, Wang W et al (2017) Colorectal cancer and colitis diagnosis using Fourier transform infrared spectroscopy and an improved k-nearest-neighbor classifier. Sensors 17:2739CrossRef
go back to reference Mathivanan S, Ji H, Simpson RJ (2010) Exosomes: extracellular organelles important in intercellular communication. J Proteomics 73:1907–1920CrossRefPubMed Mathivanan S, Ji H, Simpson RJ (2010) Exosomes: extracellular organelles important in intercellular communication. J Proteomics 73:1907–1920CrossRefPubMed
go back to reference Mihaly J, Deak R, Szigyarto IC, Bota A, Beke-Somfai T, Varga Z (2017) Characterization of extracellular vesicles by IR spectroscopy: fast and simple classification based on amide and C–H stretching vibrations. Biochim Biophys Acta Biomembr 1859:459–466CrossRefPubMed Mihaly J, Deak R, Szigyarto IC, Bota A, Beke-Somfai T, Varga Z (2017) Characterization of extracellular vesicles by IR spectroscopy: fast and simple classification based on amide and C–H stretching vibrations. Biochim Biophys Acta Biomembr 1859:459–466CrossRefPubMed
go back to reference Moore DT, Berger BW, DeGrado WF (2008) Protein-protein interactions in the membrane: sequence, structural, and biological motifs. Structure 16:991–1001CrossRefPubMedCentralPubMed Moore DT, Berger BW, DeGrado WF (2008) Protein-protein interactions in the membrane: sequence, structural, and biological motifs. Structure 16:991–1001CrossRefPubMedCentralPubMed
go back to reference Palanisamy V, Sharma S, Deshpande A, Zhou H, Gimzewski JK, Wong DT (2010) Nanostructural and transcriptomic analyses of human saliva derived exosomes. PLoS One 5:e8577CrossRefPubMedCentralPubMed Palanisamy V, Sharma S, Deshpande A, Zhou H, Gimzewski JK, Wong DT (2010) Nanostructural and transcriptomic analyses of human saliva derived exosomes. PLoS One 5:e8577CrossRefPubMedCentralPubMed
go back to reference Principe S, Hui AB, Bruce J, Sinha A, Liu FF, Kislinger T (2013) Tumor-derived exosomes and microvesicles in head and neck cancer: implications for tumor biology and biomarker discovery. Proteomics 13:1608–1623CrossRefPubMed Principe S, Hui AB, Bruce J, Sinha A, Liu FF, Kislinger T (2013) Tumor-derived exosomes and microvesicles in head and neck cancer: implications for tumor biology and biomarker discovery. Proteomics 13:1608–1623CrossRefPubMed
go back to reference Sharma S, Gillespie BM, Palanisamy V, Gimzewski JK (2011) Quantitative nanostructural and single-molecule force spectroscopy biomolecular analysis of human-saliva-derived exosomes. Langmuir 27:14394–14400CrossRefPubMedCentralPubMed Sharma S, Gillespie BM, Palanisamy V, Gimzewski JK (2011) Quantitative nanostructural and single-molecule force spectroscopy biomolecular analysis of human-saliva-derived exosomes. Langmuir 27:14394–14400CrossRefPubMedCentralPubMed
go back to reference Shield KD, Ferlay J, Jemal A, Sankaranarayanan R, Chaturvedi AK, Bray F et al (2017) The global incidence of lip, oral cavity, and pharyngeal cancers by subsite in 2012. CA Cancer J Clin 67:51–64CrossRefPubMed Shield KD, Ferlay J, Jemal A, Sankaranarayanan R, Chaturvedi AK, Bray F et al (2017) The global incidence of lip, oral cavity, and pharyngeal cancers by subsite in 2012. CA Cancer J Clin 67:51–64CrossRefPubMed
go back to reference Simonova D, Karamancheva I (2013) Application of Fourier transform infrared spectroscopy for tumor diagnosis. Biotechnol Biotechnol Equip. 27:4200–4207CrossRef Simonova D, Karamancheva I (2013) Application of Fourier transform infrared spectroscopy for tumor diagnosis. Biotechnol Biotechnol Equip. 27:4200–4207CrossRef
go back to reference Simons M, Raposo G (2009) Exosomes–vesicular carriers for intercellular communication. Curr Opin Cell Biol 21:575–581CrossRefPubMed Simons M, Raposo G (2009) Exosomes–vesicular carriers for intercellular communication. Curr Opin Cell Biol 21:575–581CrossRefPubMed
go back to reference Vlassov AV, Magdaleno S, Setterquist R, Conrad R (2012) Exosomes: current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials. Biochim Biophys Acta 1820:940–948CrossRef Vlassov AV, Magdaleno S, Setterquist R, Conrad R (2012) Exosomes: current knowledge of their composition, biological functions, and diagnostic and therapeutic potentials. Biochim Biophys Acta 1820:940–948CrossRef
go back to reference Wong DT, Nonaka T (2018) Liquid biopsy in head and neck cancer: promises and challenges. Crit Rev Oral Biol Med 97:701–708 Wong DT, Nonaka T (2018) Liquid biopsy in head and neck cancer: promises and challenges. Crit Rev Oral Biol Med 97:701–708
go back to reference Zelig U, Mordechai S, Shubinsky G, Sahu RK, Huleihel M, Leibovitz E, Nathan I, Kapelushnik J (2011) Pre-screening and follow-up of childhood acute leukemia using biochemical infrared analysis of peripheral blood mononuclear cells. Biochim Biophys Acta 1810:827–835CrossRefPubMed Zelig U, Mordechai S, Shubinsky G, Sahu RK, Huleihel M, Leibovitz E, Nathan I, Kapelushnik J (2011) Pre-screening and follow-up of childhood acute leukemia using biochemical infrared analysis of peripheral blood mononuclear cells. Biochim Biophys Acta 1810:827–835CrossRefPubMed
go back to reference Zlotogorski-Hurvitz A, Dayan D, Chaushu G, Korvala J, Salo T, Sormunen R et al (2015) Human saliva-derived exosomes: comparing methods of isolation. J Histochem Cytochem 63:181–189CrossRefPubMedCentralPubMed Zlotogorski-Hurvitz A, Dayan D, Chaushu G, Korvala J, Salo T, Sormunen R et al (2015) Human saliva-derived exosomes: comparing methods of isolation. J Histochem Cytochem 63:181–189CrossRefPubMedCentralPubMed
go back to reference Zlotogorski-Hurvitz A, Dayan D, Chaushu G, Salo T, Vered M (2016) Morphological and molecular features of oral fluid-derived exosomes: oral cancer patients versus healthy individuals. J Cancer Res Clin Oncol 142:101–110CrossRefPubMed Zlotogorski-Hurvitz A, Dayan D, Chaushu G, Salo T, Vered M (2016) Morphological and molecular features of oral fluid-derived exosomes: oral cancer patients versus healthy individuals. J Cancer Res Clin Oncol 142:101–110CrossRefPubMed
Metadata
Title
FTIR-based spectrum of salivary exosomes coupled with computational-aided discriminating analysis in the diagnosis of oral cancer
Authors
Ayelet Zlotogorski-Hurvitz
Ben Zion Dekel
Dov Malonek
Ran Yahalom
Marilena Vered
Publication date
01-03-2019
Publisher
Springer Berlin Heidelberg
Published in
Journal of Cancer Research and Clinical Oncology / Issue 3/2019
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-018-02827-6

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