title: Brain tumour differentiation: rapid stratified serum diagnostics via attenuated total reflection Fourier-transform infrared spectroscopy.
abstract: The ability to diagnose cancer rapidly with high sensitivity and specificity is essential to exploit advances in new treatments to lead significant reductions in mortality and morbidity. Current cancer diagnostic tests observing tissue architecture and specific protein expression for specific cancers suffer from inter-observer variability, poor detection rates and occur when the patient is symptomatic. A new method for the detection of cancer using 1 μl of human serum, attenuated total reflection-Fourier transform infrared spectroscopy and pattern recognition algorithms is reported using a 433 patient dataset (3897 spectra). To the best of our knowledge, we present the largest study on serum mid-infrared spectroscopy for cancer research. We achieve optimum sensitivities and specificities using a Radial Basis Function Support Vector Machine of between 80.0 and 100 % for all strata and identify the major spectral features, hence biochemical components, responsible for the discrimination within each stratum. We assess feature fed-SVM analysis for our cancer versus non-cancer model and achieve 91.5 and 83.0 % sensitivity and specificity respectively. We demonstrate the use of infrared light to provide a spectral signature from human serum to detect, for the first time, cancer versus non-cancer, metastatic cancer versus organ confined, brain cancer severity and the organ of origin of metastatic disease from the same sample enabling stratified diagnostics depending upon the clinical question asked.
authors.affiliation: WestCHEM, Department of Pure and Applied Chemistry, Technology and Innovation Centre, University of Strathclyde, 99 George Street, Glasgow, G11RD, UK.
authors.forename: James R
authors.initials: JR
authors.lastname: Hands
authors.affiliation: WestCHEM, Department of Pure and Applied Chemistry, Technology and Innovation Centre, University of Strathclyde, 99 George Street, Glasgow, G11RD, UK.|Centre for Materials Science, Division of Chemistry, University of Central Lancashire, Preston, PR12HE, UK.
authors.forename: Graeme
authors.initials: G
authors.lastname: Clemens
authors.affiliation: Digital Media Technology Laboratory, Millennium Point, City Centre Campus Birmingham City University, West Midlands, B47XG, UK.
authors.forename: Ryan
authors.initials: R
authors.lastname: Stables
authors.affiliation: Neuropathology, Lancashire Teaching Hospitals NHS Trust, Royal Preston Hospital, Sharoe Green Lane North, Preston, PR29HT, UK.
authors.forename: Katherine
authors.initials: K
authors.lastname: Ashton
authors.affiliation: The Walton Centre for Neurology and Neurosurgery, The Walton Centre NHS Trust, Lower Lane, Liverpool, L97LJ, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Brodbelt
authors.affiliation: Neuropathology, Lancashire Teaching Hospitals NHS Trust, Royal Preston Hospital, Sharoe Green Lane North, Preston, PR29HT, UK.
authors.forename: Charles
authors.initials: C
authors.lastname: Davis
authors.affiliation: Neuropathology, Lancashire Teaching Hospitals NHS Trust, Royal Preston Hospital, Sharoe Green Lane North, Preston, PR29HT, UK.
authors.forename: Timothy P
authors.initials: TP
authors.lastname: Dawson
authors.affiliation: The Walton Centre for Neurology and Neurosurgery, The Walton Centre NHS Trust, Lower Lane, Liverpool, L97LJ, UK.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Jenkinson
authors.affiliation: School of Pharmacy and Biomedical Sciences, Maudland Building, University of Central Lancashire, Preston, PR12HE, UK.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Lea
authors.affiliation: The Walton Centre for Neurology and Neurosurgery, The Walton Centre NHS Trust, Lower Lane, Liverpool, L97LJ, UK.
authors.forename: Carol
authors.initials: C
authors.lastname: Walker
authors.affiliation: WestCHEM, Department of Pure and Applied Chemistry, Technology and Innovation Centre, University of Strathclyde, 99 George Street, Glasgow, G11RD, UK. matthew.baker@strath.ac.uk.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Baker
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D014408:Biomarkers, Tumor / Q000097:blood*; D001932:Brain Neoplasms / Q000097:blood* / Q000175:diagnosis*; D016022:Case-Control Studies; D002454:Cell Differentiation; D055088:Early Detection of Cancer; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D011379:Prognosis; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods*; D060388:Support Vector Machine; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor
keywords: ATR-FTIR; Cancer; Diagnostics; Glioma; Rapid; Serum; Spectroscopy