Eyal Barlev1,2, Udi Zelig3, Omri Bar4, Cheli Segev4, Shaul Mordechai5, Joseph Kapelushnik6,7, Ilana Nathan8,9, Felix Flomen4, Hanoch Kashtan10, Ram Dickman2,11, Osnat Madhala-Givon1,2, Nir Wasserberg1,2. 1. Department of Surgery B, Rabin Medical Center, Beilinson Campus, Petach Tikva, Israel. 2. Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 3. Todos Medical Ltd, 1 HaMada St, 76703, Rehovot, Israel. udi@todosmedical.com. 4. Todos Medical Ltd, 1 HaMada St, 76703, Rehovot, Israel. 5. Department of Physics, Ben-Gurion University of the Negev, Beer-Sheva, Israel. 6. Pediatric Hemato-Oncology Unit, Soroka University Medical Center, Beer-Sheva, Israel. 7. Faculty of Medicine, Ben-Gurion University of the Negev, Beer-Sheva, Israel. 8. Department of Clinical Biochemistry, Ben-Gurion University of the Negev, Beer-Sheva, Israel. 9. Institute of Hematology, Soroka University Medical Center, Beer-Sheva, Israel. 10. Division of General Surgery, Rabin Medical Center, Beilinson Campus, Petach Tikva, Israel. 11. Department of Gastroenterology, Rabin Medical Center, Beilinson Campus, Petach Tikva, Israel.
Abstract
BACKGROUND: Early detection of colorectal cancer (CRC) can reduce mortality and morbidity. Current screening methods include colonoscopy and stool tests, but a simple low-cost blood test would increase compliance. This preliminary study assessed the utility of analyzing the entire bio-molecular profile of peripheral blood mononuclear cells (PBMCs) and plasma using Fourier transform infrared (FTIR) spectroscopy for early detection of CRC. METHODS: Blood samples were prospectively collected from 62 candidates for CRC screening/diagnostic colonoscopy or surgery for colonic neoplasia. PBMCs and plasma were separated by Ficoll gradient, dried on zinc selenide slides, and placed under a FTIR microscope. FTIR spectra were analyzed for biomarkers and classified by principal component and discriminant analyses. Findings were compared among diagnostic groups. RESULTS: Significant changes in multiple bands that can serve as CRC biomarkers were observed in PBMCs (p = ~0.01) and plasma (p = ~0.0001) spectra. There were minor but statistically significant differences in both blood components between healthy individuals and patients with benign polyps. Following multivariate analysis, the healthy individuals could be well distinguished from patients with CRC, and the patients with benign polyps were mostly distributed as a distinct subgroup within the overlap region. Leave-one-out cross-validation for evaluating method performance yielded an area under the receiver operating characteristics curve of 0.77, with sensitivity 81.5% and specificity 71.4%. CONCLUSIONS: Joint analysis of the biochemical profile of two blood components rather than a single biomarker is a promising strategy for early detection of CRC. Additional studies are required to validate our preliminary clinical results.
BACKGROUND: Early detection of colorectal cancer (CRC) can reduce mortality and morbidity. Current screening methods include colonoscopy and stool tests, but a simple low-cost blood test would increase compliance. This preliminary study assessed the utility of analyzing the entire bio-molecular profile of peripheral blood mononuclear cells (PBMCs) and plasma using Fourier transform infrared (FTIR) spectroscopy for early detection of CRC. METHODS: Blood samples were prospectively collected from 62 candidates for CRC screening/diagnostic colonoscopy or surgery for colonic neoplasia. PBMCs and plasma were separated by Ficoll gradient, dried on zinc selenide slides, and placed under a FTIR microscope. FTIR spectra were analyzed for biomarkers and classified by principal component and discriminant analyses. Findings were compared among diagnostic groups. RESULTS: Significant changes in multiple bands that can serve as CRC biomarkers were observed in PBMCs (p = ~0.01) and plasma (p = ~0.0001) spectra. There were minor but statistically significant differences in both blood components between healthy individuals and patients with benign polyps. Following multivariate analysis, the healthy individuals could be well distinguished from patients with CRC, and the patients with benign polyps were mostly distributed as a distinct subgroup within the overlap region. Leave-one-out cross-validation for evaluating method performance yielded an area under the receiver operating characteristics curve of 0.77, with sensitivity 81.5% and specificity 71.4%. CONCLUSIONS: Joint analysis of the biochemical profile of two blood components rather than a single biomarker is a promising strategy for early detection of CRC. Additional studies are required to validate our preliminary clinical results.
Authors: A D Toll; D Fabius; T Hyslop; E Pequignot; A J DiMarino; A Infantolino; J P Palazzo Journal: Colorectal Dis Date: 2011-04 Impact factor: 3.788
Authors: Elias Gounaris; Nichole R Blatner; Kristen Dennis; Fay Magnusson; Michael F Gurish; Terry B Strom; Philipp Beckhove; Fotini Gounari; Khashayarsha Khazaie Journal: Cancer Res Date: 2009-07-01 Impact factor: 12.701
Authors: Benjamin Bird; Milos Miljkovic; Melissa J Romeo; Jennifer Smith; Nicholas Stone; Michael W George; Max Diem Journal: BMC Clin Pathol Date: 2008-08-29
Authors: Tom Grunert; Rebecca Herzog; Florian M Wiesenhofer; Andreas Vychytil; Monika Ehling-Schulz; Klaus Kratochwill Journal: Biomolecules Date: 2020-06-26