Segregation of human prostate tissues classified high-risk (UK) versus low-risk (India) for adenocarcinoma using Fourier-transform infrared or Raman microspectroscopy coupled with discriminant analysis

AbstractVibrational spectroscopy techniques can be applied to identify a susceptibility-to-adenocarcinoma biochemical signature. A sevenfold difference in incidence of prostate adenocarcinoma (CaP) remains apparent amongst populations of low- (e.g. India) compared with high-risk (e.g. UK) regions, with migrant studies implicating environmental and/or lifestyle/dietary causative factors. This study set out to determine the biospectroscopy-derived spectral differences between risk-associated cohorts to CaP. Benign prostate tissues were obtained using transurethral resection from high-risk (n = 11, UK) and low-risk (n = 14, India) cohorts. Samples were analysed using attenuated total reflection Fourier-transform infrared (FTIR) spectroscopy, FTIR microspectroscopy and Raman microspectroscopy. Spectra were subsequently processed within the biochemical cell region (1,800−1–500 cm–1) employing principal component analysis (PCA) and linear discriminant analysis (LDA) to determine whether wavenumber–absorbance/intensity relationships might reveal biochemical differences associated with region-specific susceptibility to CaP. PCA-LDA scores and corresponding cluster vector plots identified pivotal segregating biomarkers as 1,582 cm−1 (Amide I/II trough); 1,551 cm−1 (Amide II); 1,667 cm−1 (Amide I); 1,080 cm−1 (DNA/RNA); 1,541 cm−1 (Amide II); 1,468 cm−1 (protein); 1,232 cm−1 (DNA); 1,003 cm−1 (phenylalanine); 1,632 cm−1 [right-hand side (RHS) Amide I] for glandular epithelium (P < 0.0001) and 1,663 cm−1 (Amide I); 1,624 cm−1 (RHS Amide I); 1,126 cm−1 (RNA); 1,761, 1,782, 1,497 cm−1 (RHS Amide II); 1,003 cm−1 (phenylalanine); and 1,624 cm−1 (RHS Amide I) for adjacent stroma (P < 0.0001). Primarily protein secondary structure variations were biomolecular markers responsible for cohort segregation with DNA alterations exclusively located in the glandular epithelial layers. These biochemical differences may lend vital insights into the aetiology of CaP. FigureThe first study to apply biospectroscopy techniques to identify the underlying differences in the aetiology of prostate cancer between low- (India) compared to high-risk (UK) cohorts

[1]  P. Singh,et al.  A potential paradox in prostate adenocarcinoma progression: oestrogen as the initiating driver. , 2008, European journal of cancer.

[2]  N. Polissar,et al.  Cancer-related changes in prostate DNA as men age and early identification of metastasis in primary prostate tumors , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[3]  F. Martin,et al.  Discrimination of zone-specific spectral signatures in normal human prostate using Raman spectroscopy. , 2010, The Analyst.

[4]  P. Basu,et al.  Quantified gene expression levels for phase I/II metabolizing enzyme and estrogen receptor levels in benign prostate from cohorts designated as high-risk (UK) versus low-risk (India) for adenocarcinoma at this organ site: a preliminary study. , 2010, Asian journal of andrology.

[5]  Francis L Martin,et al.  Distinguishing cell types or populations based on the computational analysis of their infrared spectra , 2010, Nature Protocols.

[6]  Francis L Martin,et al.  Tracking the cell hierarchy in the human intestine using biochemical signatures derived by mid-infrared microspectroscopy. , 2009, Stem cell research.

[7]  Francis L Martin,et al.  Derivation of a subtype-specific biochemical signature of endometrial carcinoma using synchrotron-based Fourier-transform infrared microspectroscopy. , 2009, Cancer letters.

[8]  Eva Frei,et al.  Constitutive expression of bioactivating enzymes in normal human prostate suggests a capability to activate pro‐carcinogens to DNA‐damaging metabolites , 2010, The Prostate.

[9]  Barbara H. Stuart,et al.  Infrared Spectroscopy: Fundamentals and Applications: Stuart/Infrared Spectroscopy: Fundamentals and Applications , 2005 .

[10]  Joe M. Byrne,et al.  Raman Spectroscopic Evaluation of Efficacy of Current Paraffin Wax Section Dewaxing Agents , 2005, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[11]  M. Teh,et al.  Diagnostic potential of near-infrared Raman spectroscopy in the stomach: differentiating dysplasia from normal tissue , 2008, British Journal of Cancer.

[12]  Francis L Martin Shining a new light into molecular workings , 2011, Nature Methods.

[13]  F. Martin,et al.  The initiation of breast and prostate cancer. , 2002, Carcinogenesis.

[14]  H. Barr,et al.  Raman spectroscopy for identification of epithelial cancers. , 2004, Faraday discussions.

[15]  Francis L Martin,et al.  Syrian hamster embryo (SHE) assay (pH 6.7) coupled with infrared spectroscopy and chemometrics towards toxicological assessment. , 2010, The Analyst.

[16]  E. Noel,et al.  Differential gene expression in the peripheral zone compared to the transition zone of the human prostate gland , 2008, Prostate Cancer and Prostatic Diseases.

[17]  Cyril Petibois,et al.  FT-IR spectral imaging of blood vessels reveals protein secondary structure deviations induced by tumor growth , 2008, Analytical and bioanalytical chemistry.

[18]  Virgilia Macias,et al.  High-resolution Fourier-transform infrared chemical imaging with multiple synchrotron beams , 2011, Nature Methods.

[19]  Andrew J Berger,et al.  Method for automated background subtraction from Raman spectra containing known contaminants. , 2009, The Analyst.

[20]  Francis L Martin,et al.  Infrared spectroscopy with multivariate analysis potentially facilitates the segregation of different types of prostate cell. , 2006, Biophysical journal.

[21]  B. Stuart Infrared Spectroscopy , 2004, Analytical Techniques in Forensic Science.

[22]  J. McNeal,et al.  Normal histology of the prostate. , 1988, The American journal of surgical pathology.

[23]  Andrew J. Vickers,et al.  Prostate-specific antigen and prostate cancer: prediction, detection and monitoring , 2008, Nature Reviews Cancer.

[24]  Henrik Grönberg,et al.  Prostate cancer epidemiology , 2003, The Lancet.

[25]  N. Clarke,et al.  FTIR-based spectroscopic analysis in the identification of clinically aggressive prostate cancer , 2008, British Journal of Cancer.

[26]  E. Crawford,et al.  Understanding the epidemiology, natural history, and key pathways involved in prostate cancer. , 2009, Urology.

[27]  Francis L Martin,et al.  IR microspectroscopy: potential applications in cervical cancer screening. , 2007, Cancer letters.

[28]  A. Chokkalingam,et al.  Prostate cancer epidemiology. , 2006, Frontiers in bioscience : a journal and virtual library.

[29]  J Dwyer,et al.  Applications of Fourier transform infrared microspectroscopy in studies of benign prostate and prostate cancer. A pilot study , 2003, The Journal of pathology.

[30]  Ganesh D. Sockalingum,et al.  Raman spectral imaging of single cancer cells: probing the impact of sample fixation methods , 2010, Analytical and bioanalytical chemistry.

[31]  G. Stemmermann,et al.  Geographic pathology of latent prostatic carcinoma , 1982, International journal of cancer.

[32]  R. Sinha,et al.  Cancer incidence rates among South Asians in four geographic regions: India, Singapore, UK and US. , 2008, International journal of epidemiology.

[33]  S. Hayward,et al.  Role of the stromal microenvironment in carcinogenesis of the prostate , 2003, International journal of cancer.

[34]  D. Lin-Vien The Handbook of Infrared and Raman Characteristic Frequencies of Organic Molecules , 1991 .

[35]  G. Ayala,et al.  Reactive stroma in human prostate cancer: induction of myofibroblast phenotype and extracellular matrix remodeling. , 2002, Clinical cancer research : an official journal of the American Association for Cancer Research.