| Autor: |
Deng X; Department of Physics, The University of British Columbia Kelowna, Canada., Milligan K; Department of Physics, The University of British Columbia Kelowna, Canada., Ali-Adeeb R; Department of Physics, The University of British Columbia Kelowna, Canada., Shreeves P; Department of Statistics, The University of British Columbia, Kelowna, Canada., Brolo A; Department of Chemistry, University of Victoria, Victoria, Canada., Lum JJ; Department of Biochemistry and Microbiology, University of Victoria, Victoria, Canada.; Trev and Joyce Deeley Research Centre, BC Cancer, Victoria, Canada., Andrews JL; Department of Statistics, The University of British Columbia, Kelowna, Canada., Jirasek A; Department of Physics, The University of British Columbia Kelowna, Canada. |
| Abstrakt: |
Raman spectroscopy is a non-invasive optical technique that can be used to investigate biochemical information embedded in cells and tissues exposed to ionizing radiation used in cancer therapy. Raman spectroscopy could potentially be incorporated in personalized radiation treatment design as a tool to monitor radiation response in at the metabolic level. However, tracking biochemical dynamics remains challenging for Raman spectroscopy. Here we developed a novel analytical framework by combining group and basis restricted non-negative matrix factorization and random forest (GBR-NMF-RF). This framework can monitor radiation response profiles in different molecular histotypes and biochemical dynamics in irradiated breast cancer cells. Five subtypes of; human breast cancer (MCF-7, BT-474, MDA-MB-230, and SK-BR-3) and normal cells derived from human breast tissue (MCF10A) which had been exposed to ionizing radiation were tested in this framework. Reference Raman spectra of 20 biochemicals were collected and used as the constrained Raman biomarkers in the GBR-NMF-RF framework. We obtained scores for individual biochemicals corresponding to the contribution of each Raman reference spectrum to each spectrum obtained from the five cell types. A random forest classifier was then fitted to the chemical scores for performing molecular histotype classifications (HER2, PR, ER, Ki67, and cancer versus non-cancer) and assessing the importance of the Raman biochemical basis spectra for each classification test. Overall, the GBR-NMF-RF framework yields classification results with high accuracy (>97%), high sensitivity (>97%), and high specificity (>97%). Variable importance calculated in the random forest model indicated high contributions from glycogen and lipids (cholesterol, phosphatidylserine, and stearic acid) in molecular histotype classifications. |
