title: Raman fiber-optical method for colon cancer detection: Cross-validation and outlier identification approach.
abstract: Endoscopy plays a major role in early recognition of cancer which is not externally accessible and therewith in increasing the survival rate. Raman spectroscopic fiber-optical approaches can help to decrease the impact on the patient, increase objectivity in tissue characterization, reduce expenses and provide a significant time advantage in endoscopy. In gastroenterology an early recognition of malign and precursor lesions is relevant. Instantaneous and precise differentiation between adenomas as precursor lesions for cancer and hyperplastic polyps on the one hand and between high and low-risk alterations on the other hand is important. Raman fiber-optical measurements of colon biopsy samples taken during colonoscopy were carried out during a clinical study, and samples of adenocarcinoma (22), tubular adenomas (141), hyperplastic polyps (79) and normal tissue (101) from 151 patients were analyzed. This allows us to focus on the bioinformatic analysis and to set stage for Raman endoscopic measurements. Since spectral differences between normal and cancerous biopsy samples are small, special care has to be taken in data analysis. Using a leave-one-patient-out cross-validation scheme, three different outlier identification methods were investigated to decrease the influence of systematic errors, like a residual risk in misplacement of the sample and spectral dilution of marker bands (esp. cancerous tissue) and therewith optimize the experimental design. Furthermore other validations methods like leave-one-sample-out and leave-one-spectrum-out cross-validation schemes were compared with leave-one-patient-out cross-validation. High-risk lesions were differentiated from low-risk lesions with a sensitivity of 79%, specificity of 74% and an accuracy of 77%, cancer and normal tissue with a sensitivity of 79%, specificity of 83% and an accuracy of 81%. Additionally applied outlier identification enabled us to improve the recognition of neoplastic biopsy samples.
authors.affiliation: Department of Biophysics and Protein Research Unit Europe (PURE), Ruhr University Bochum, ND/04 Nord, 44780 Bochum, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Petersen
authors.affiliation: University Hospital Knappschaftskrankenhaus Bochum, In der Schornau 23-25, 44892 Bochum, Germany; Department of Gastroenterology/Hepatology, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil GmbH, Bürkle-de-la-Camp-Platz 1, 44789 Bochum, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Naveed
authors.affiliation: University Hospital Knappschaftskrankenhaus Bochum, In der Schornau 23-25, 44892 Bochum, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Ragheb
authors.affiliation: Department of Biophysics and Protein Research Unit Europe (PURE), Ruhr University Bochum, ND/04 Nord, 44780 Bochum, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Niedieker
authors.affiliation: Department of Biophysics and Protein Research Unit Europe (PURE), Ruhr University Bochum, ND/04 Nord, 44780 Bochum, Germany.
authors.forename: S F
authors.initials: SF
authors.lastname: El-Mashtoly
authors.affiliation: Department of Gastroenterology/Hepatology, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil GmbH, Bürkle-de-la-Camp-Platz 1, 44789 Bochum, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Brechmann
authors.affiliation: Department of Biophysics and Protein Research Unit Europe (PURE), Ruhr University Bochum, ND/04 Nord, 44780 Bochum, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Kötting
authors.affiliation: University Hospital Knappschaftskrankenhaus Bochum, In der Schornau 23-25, 44892 Bochum, Germany; Department of Gastroenterology/Hepatology, Berufsgenossenschaftliches Universitätsklinikum Bergmannsheil GmbH, Bürkle-de-la-Camp-Platz 1, 44789 Bochum, Germany.
authors.forename: W H
authors.initials: WH
authors.lastname: Schmiegel
authors.affiliation: Department of Biophysics and Protein Research Unit Europe (PURE), Ruhr University Bochum, ND/04 Nord, 44780 Bochum, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Freier
authors.affiliation: University Hospital Knappschaftskrankenhaus Bochum, In der Schornau 23-25, 44892 Bochum, Germany. Electronic address: cpox@sjs-bremen.de.
authors.forename: C
authors.initials: C
authors.lastname: Pox
authors.affiliation: Department of Biophysics and Protein Research Unit Europe (PURE), Ruhr University Bochum, ND/04 Nord, 44780 Bochum, Germany. Electronic address: gerwert@bph.ruhr-uni-bochum.de.
authors.forename: K
authors.initials: K
authors.lastname: Gerwert
mesh_terms: D001706:Biopsy; D003106:Colon / Q000000981:diagnostic imaging; D003110:Colonic Neoplasms / Q000000981:diagnostic imaging* / Q000601:surgery*; D003113:Colonoscopy / Q000379:methods*; D019295:Computational Biology; D006801:Humans; D012680:Sensitivity and Specificity; D013059:Spectrum Analysis, Raman / Q000379:methods*
keywords: Bioinformatics; Cancer recognition; Colonoscopy; Label-free; Raman spectroscopy