Biomarkers spectral subspace for cancer detection

Abstract. A novel approach to cancer detection in biomarkers spectral subspace (BSS) is proposed. The basis spectra of the subspace spanned by fluorescence spectra of biomarkers are obtained by the Gram-Schmidt method. A support vector machine classifier (SVM) is trained in the subspace. The spectrum of a sample tissue is projected onto and is classified in the subspace. In addition to sensitivity and specificity, the metrics of positive predictivity, Score1, maximum Score1, and accuracy (AC) are employed for performance evaluation. The proposed BSS using SVM is applied to breast cancer detection using four biomarkers: collagen, NADH, flavin, and elastin, with 340-nm excitation. It is found that the BSS SVM outperforms the approach based on multivariate curve resolution (MCR) using SVM and achieves the best performance of principal component analysis (PCA) using SVM among all combinations of PCs. The descent order of efficacy of the four biomarkers in the breast cancer detection of this experiment is collagen, NADH, elastin, and flavin. The advantage of BSS is twofold. First, all diagnostically useful information of biomarkers for cancer detection is retained while dimensionality of data is significantly reduced to obviate the curse of dimensionality. Second, the efficacy of biomarkers in cancer detection can be determined.

[1]  K. Badizadegan,et al.  NAD(P)H and collagen as in vivo quantitative fluorescent biomarkers of epithelial precancerous changes. , 2002, Cancer research.

[2]  B. Kowalski,et al.  Selectivity, local rank, three‐way data analysis and ambiguity in multivariate curve resolution , 1995 .

[3]  John F. Mustard,et al.  Spectral unmixing , 2002, IEEE Signal Process. Mag..

[4]  Wei Zheng,et al.  High wavenumber Raman spectroscopy for in vivo detection of cervical dysplasia. , 2009, Analytical chemistry.

[5]  R. Alfano,et al.  Native Fluorescence Spectroscopic Evaluation of Chemotherapeutic Effects on Malignant Cells using Nonnegative Matrix Factorization Analysis , 2011, Technology in cancer research & treatment.

[6]  M. Geyp,et al.  Breast tumour cell-induced down-regulation of type I collagen mRNA in fibroblasts , 1999, British Journal of Cancer.

[7]  D. Choy,et al.  Fluorescence spectra from cancerous and normal human breast and lung tissues , 1987, Annual Meeting Optical Society of America.

[8]  Yang Pu,et al.  Changes of collagen and nicotinamide adenine dinucleotide in human cancerous and normal prostate tissues studied using native fluorescence spectroscopy with selective excitation wavelength. , 2010, Journal of biomedical optics.

[9]  L. Citi,et al.  PhysioNet 2012 Challenge: Predicting mortality of ICU patients using a cascaded SVM-GLM paradigm , 2012, 2012 Computing in Cardiology.

[10]  Corinna Cortes,et al.  Support-Vector Networks , 1995, Machine Learning.

[11]  Romà Tauler,et al.  Multivariate Curve Resolution (MCR) from 2000: Progress in Concepts and Applications , 2006 .

[12]  R Richards-Kortum,et al.  Understanding the contributions of NADH and collagen to cervical tissue fluorescence spectra: modeling, measurements, and implications. , 2001, Journal of biomedical optics.

[13]  Marti A. Hearst Trends & Controversies: Support Vector Machines , 1998, IEEE Intell. Syst..

[14]  R. Kessler,et al.  Online UV–visible spectroscopy and multivariate curve resolution as powerful tool for model-free investigation of laccase-catalysed oxidation , 2008, Analytical and bioanalytical chemistry.

[15]  H. Bloom,et al.  Histological Grading and Prognosis in Breast Cancer , 1957, British Journal of Cancer.

[16]  J. Eisinger,et al.  Front-face fluorometry of liquid samples. , 1979, Analytical biochemistry.

[17]  R. Alfano,et al.  Laser induced fluorescence spectroscopy from native cancerous and normal tissue , 1984 .