Cell-free DNA as a biomarker for prostate cancer: elevated concentration and decreased fragment size

Chen, E.; Cario, C. L.; Leong, L.; Lopez, K.; Marquez, C.; Chu, C.; Li, P. S.; Oropeza, E.; Tenggara, I.; Cowan, J.; Simko, J. P.; Chan, J. M.; Friedlander, T.; Wyatt, A. W.; Aggarwal, R.; Paris, P. L.; Carroll, P. R.; Feng, F.; Witte, J. S.

doi:10.1101/2020.07.26.215020

bioRxiv · 10.1101/2020.07.26.215020

Cell-free DNA as a biomarker for prostate cancer: elevated concentration and decreased fragment size

Chen, E.·Cario, C. L.·Leong, L.·Lopez, K.·Marquez, C.·Chu, C.·Li, P. S.·Oropeza, E.·Tenggara, I.·Cowan, J.·Simko, J. P.·Chan, J. M.·Friedlander, T.·Wyatt, A. W.·Aggarwal, R.·Paris, P. L.·Carroll, P. R.·Feng, F.·Witte, J. S.

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Abstract

PurposeProstate cancer is the most commonly diagnosed neoplasm in American men. Although existing biomarkers may detect localized prostate cancer, additional strategies are necessary for improving detection and identifying aggressive disease that may require further intervention. One promising, minimally invasive biomarker is cell-free DNA (cfDNA), which consist of short DNA fragments released into circulation by dying or lysed cells that may reflect underlying cancer. Here we investigated whether differences in cfDNA concentration and cfDNA fragment size could improve the sensitivity for detecting more advanced and aggressive prostate cancer. Materials and MethodsThis study included 268 individuals: 34 healthy controls, 112 men with localized prostate cancer who underwent radical prostatectomy (RP), and 122 men with metastatic castration-resistant prostate cancer (mCRPC). Plasma cfDNA concentration and fragment size were quantified with the Qubit 3.0 and the 2100 Bioanalyzer. The potential relationship between cfDNA concentration or fragment size and localized or mCRPC prostate cancer was evaluated with descriptive statistics, logistic regression, and area under the curve analysis with cross-validation. ResultsPlasma cfDNA concentrations were elevated in mCRPC patients in comparison to localized disease (OR5 ng/mL = 1.34, P = 0.027) or to being a control (OR5 ng/mL = 1.69, P = 0.034). Decreased average fragment size was associated with an increased risk of localized disease compared to controls (OR5bp = 0.77, P = 0.0008). ConclusionThis study suggests that cfDNA concentration and average cfDNA fragment size may provide a quick, cost-effective approach to help determine which patients will benefit most from further screening and/or disease monitoring to help improve prostate cancer outcomes.

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Chen, E., Cario, C. L., Leong, L., Lopez, K., Marquez, C., Chu, C., Li, P. S., Oropeza, E., Tenggara, I., Cowan, J., Simko, J. P., Chan, J. M., Friedlander, T., Wyatt, A. W., Aggarwal, R., Paris, P. L., Carroll, P. R., Feng, F., Witte, J. S.. 2020-07-26. Cell-free DNA as a biomarker for prostate cancer: elevated concentration and decreased fragment size. https://doi.org/10.1101/2020.07.26.215020

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