Cell-free DNA in the blood as a solid tumor biomarker--a critical appraisal of the literature

Abstract

Circulating cell-free DNA (cfDNA) has been suggested as a cancer biomarker. Several studies assessed the usefulness of quantitative and qualitative tumor-specific alterations of cfDNA, such as DNA strand integrity, frequency of mutations, abnormalities of microsatellites, and methylation of genes, as diagnostic, prognostic, and monitoring markers in cancer patients. Most of the papers that could be evaluated in this review resulted in a positive conclusion. However, methodical diversity without the traceability of data and differently designed and often underpowered studies resulted in divergent results between studies. In addition, the limited diagnostic sensitivity and specificity of cfDNA alterations temper the effusive hope of novel tumor markers, raising similar issues as those for other tumor markers. To validate the actual clinical validity of various cfDNA alterations as potential cancer biomarkers in practice for individual tumor types, the main problems of the observed uncertainties must be considered in future studies. These include methodical harmonization concerning sample collection, processing, and analysis with the traceability of measurement results as well as the realization of well-designed prospective studies based on power analysis and sample size calculations.