Study on glycoprotein terahertz time-domain spectroscopy based on composite multiscale entropy feature extraction method.

Tumor genesis is accompanied by glycosylation of related proteins. Glycoprotein is usually regarded as a tumor marker since glycoproteins are consumed remarkably more by the cancer cells than the normal ones. In this paper, the terahertz time-domain attenuated total reflection (ATR) technique is applied to inspect the glycoprotein solution from a concentration gradient of 0.2 mg/ml to 50 mg/ml. A significant nonlinear relationship between the absorption coefficient and the concentrations has been discovered. The influence of the dynamical hydration shell around glycoprotein molecules on the absorption coefficient is discussed and the phenomenon is explained by the concepts of THz excess and THz defect. In order to identify glycoproteins, features are obtained by composite multiscale entropy (CMSE) method and clustered by the K-means algorithm. The results indicate that features extracted by the CMSE method are better than the Principal Component Analysis (PCA) method in both specificity and sensitivity of recognition. Meanwhile, the absorption coefficient and dielectric loss angle tangent are more suitable for qualitative identification. Research shows that the CMSE method has important directive significance for analyzing glycoprotein terahertz spectroscopy. And it has the potential for glycoprotein related tumor markers identification using terahertz technology in medical applications.

[1]  Dibo Hou,et al.  Terahertz spectroscopic investigation of human gastric normal and tumor tissues , 2014, Physics in medicine and biology.

[2]  U. Menon,et al.  Evidence of Altered Glycosylation of Serum Proteins Prior to Pancreatic Cancer Diagnosis , 2017, International journal of molecular sciences.

[3]  Wenhui Fan,et al.  Application of terahertz spectroscopy and molecular modeling in isomers investigation: Glucose and fructose , 2012 .

[4]  Ma Qian-Li,et al.  Multiscale entropy based study of the pathological time series , 2008 .

[5]  Naoshi Kondo,et al.  Evaluation of the hydration state of saccharides using terahertz time-domain attenuated total reflection spectroscopy. , 2013, Food chemistry.

[6]  Hung T. Nguyen,et al.  A Dielectric Model of Human Breast Tissue in Terahertz Regime , 2015, IEEE Transactions on Biomedical Engineering.

[7]  Daniel F Hayes,et al.  Cancer biomarkers , 2012, Molecular oncology.

[8]  Martina Havenith,et al.  Terahertz Dance of Proteins and Sugars with Water , 2009 .

[9]  Gianfelice Cinque,et al.  Analysis of the hydration water around bovine serum albumin using terahertz coherent synchrotron radiation. , 2014, The journal of physical chemistry. A.

[10]  Emma Pickwell-MacPherson,et al.  Composite multiscale entropy analysis of reflective terahertz signals for biological tissues. , 2017, Optics express.

[11]  B. Stewart,et al.  World cancer report 2014. , 2014 .

[12]  Madalena Costa,et al.  Multiscale entropy analysis of biological signals. , 2005, Physical review. E, Statistical, nonlinear, and soft matter physics.

[13]  Ke Yang,et al.  Biomedical Applications of Terahertz Spectroscopy and Imaging. , 2016, Trends in biotechnology.

[14]  Madalena Costa,et al.  Multiscale entropy analysis of complex physiologic time series. , 2002, Physical review letters.

[15]  Dibo Hou,et al.  Terahertz spectral unmixing based method for identifying gastric cancer. , 2018, Physics in medicine and biology.

[16]  Terahertz ATR Spectroscopy of Liquids Using THz-Wave Parametric Sources , 2007, 2007 Conference on Lasers and Electro-Optics - Pacific Rim.

[17]  Wenxue Hong,et al.  [Automatic Classification of Epileptic Electroencephalogram Signal Based on Improved Multivariate Multiscale Entropy]. , 2015, Sheng wu yi xue gong cheng xue za zhi = Journal of biomedical engineering = Shengwu yixue gongchengxue zazhi.

[18]  Yibin Ying,et al.  Extraordinary sensitivity enhancement by metasurfaces in terahertz detection of antibiotics , 2015, Scientific Reports.

[19]  Zhaohui Zhang,et al.  [The Lambert-Beer's law characterization of formal analysis in Terahertz spectrum quantitative testing]. , 2013, Guang pu xue yu guang pu fen xi = Guang pu.

[20]  S. Villanueva-Rodríguez,et al.  Hydration shells of carbohydrate polymers studied by calorimetry and terahertz spectroscopy. , 2019, Food chemistry.

[21]  Xi-Cheng Zhang,et al.  Self-referenced method for terahertz wave time-domain spectroscopy. , 2011, Optics letters.

[22]  S. Pinho,et al.  Glycosylation in cancer: mechanisms and clinical implications , 2015, Nature Reviews Cancer.

[23]  Z. Geng,et al.  A Route to Terahertz Metamaterial Biosensor Integrated with Microfluidics for Liver Cancer Biomarker Testing in Early Stage , 2017, Scientific Reports.

[24]  M. Havenith,et al.  Perspective: Watching low-frequency vibrations of water in biomolecular recognition by THz spectroscopy. , 2015, The Journal of chemical physics.

[25]  R. Brand,et al.  Spectral library‐based glycopeptide analysis–detection of circulating galectin‐3 binding protein in pancreatic cancer , 2017, Proteomics. Clinical applications.

[26]  Daniel F Hayes,et al.  ASCO 2006 update of recommendations for the use of tumor markers in gastrointestinal cancer. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[27]  Kai Liu,et al.  Recent advances in terahertz technology for biomedical applications. , 2017, Quantitative imaging in medicine and surgery.

[28]  N. Taniguchi Toward Cancer Biomarker Discovery using the Glycomics Approach , 2008, Proteomics.

[29]  Hong-Liang Cui,et al.  Label-free detection of anti-estrogen receptor alpha and its binding with estrogen receptor peptide alpha by terahertz spectroscopy , 2017 .

[30]  R. Bast,et al.  American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. , 2007, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[31]  Kejia Wang,et al.  Classification and identification of molecules through factor analysis method based on terahertz spectroscopy. , 2018, Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.

[32]  Fang Wang,et al.  Terahertz spectra of DNA nucleobase crystals: A joint experimental and computational study. , 2017, Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.