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UV-Induced DNA damage response in blood cells as a potential method for cancer detection

University of British Columbia

Early detection of cancer is the single best parameter predicting positive outcome for patients. Detection of cancer in the early disease stages usually requires a combination of tests that are often expensive for our health care systems and invasive for the patients. Hence, developing a simple crude non-invasive liquid biopsy test able to detect cancer would be of utmost significance. This proof of concept case-study aimed to investigate the potential of developing an assay to distinguish between cancer patients and healthy individuals based on their immune cells’ responses to ultraviolet light exposure. The new technology of ultraviolet light emitting diodes (UV-LEDs) makes it possible to provide exact irradiating doses and wavelengths, superior to traditional UV lamp-based light sources for these types of studies. The human leukemia cell line, Jurkat, was used as a model to develop and improve the assay. Expression and phosphorylation of the DNA repair marker histone 2AX (γH2AX), was analyzed in 18 human blood samples after UV irradiation: 9 samples from prostate cancer patients all undergoing Radical Prostatectomy treatment with no history of neoadjuvant therapy and 9 control samples from healthy individuals. The expression of γH2AX was amplified 6 hours after exposure in all samples and the dose (3 mJ/cm2) and the wavelength (285 nm) chosen for this study induced cell death in blood cells after 24 hours. The median of the normalized γH2AX expression was significantly different between prostate cancer (PCa) patients and healthy donors (p<0.01). Receiver operating characteristic (ROC) analysis of normalized γH2AX expression in peripheral blood monocyte cells (PBMCs) isolated from PCa patients vs. PBMCs isolated from healthy donors gave an area under the curve (AUC) of 0.9306 (P=0.0029). The method described in this study had sensitivities, specificities, and an AUC comparable to current cancer detection assays currently in clinical use. As such, this method could potentially provide a supplement to current gold standard early cancer detection applications for the benefit of patients and our health care economy.

Text

2021-01-31

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/69791

Chemical and Biological Engineering

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/