The Length and Distribution of Plasma Cell-Free DNA Fragments in Stroke Patients

Abstract

A number of studies have shown that plasma cell-free DNA is closely related to the risk of stroke, but the fragmentation status of plasma cell-free DNA and its clinical application value in ischemic stroke are still unclear. In this study, 48 patients with new ischemic stroke and 20 healthy subjects were enrolled. The second-generation high-throughput sequencing technique was used to study the plasma cell-free fragment length and regional distribution of the subjects. As noted in our results, the ratio of plasma cell-free DNA fragments in the disease group was significantly greater than that of the healthy group in the 300–400 bp range; conversely for fragments at the 75–250 bp range, the ratio of plasma cell-free DNA fragments in the patient group was apparently lower than that of the healthy group. In-depth analysis of the proportion of fragments distributed on each component of the genome was carried out. Our results recorded that the plasma cell-free DNA fragments in the disease group were inclined to the EXON, CpG islands, and ALU regions in contrast to that of the healthy group. In particular, fragments within the 300–400 bp range of the disease group were enrichment in the regions of EXON, INTRON, INTERGENIC, LINE, Fragile, ALU, and CpG islands. In summary, our findings suggested that the intracellular DNA degradation profiles could be applied to distinguish the stroke group and the healthy group, which provided a theoretical basis for the clinical diagnosis and prognosis of stroke by profiling the characteristic of plasma cell-free DNA fragments.

Total and endothelial cell-derived cell-free DNA in blood plasma does not change during menstruation

“…It is also possible that we did not observe an increase in cfDNA because menstruation leads to DNA fragmentation to a size that cannot be amplified by the ALU-115 and the endothelial cell specific primers, which create 115 bp and 96 bp products respectively. It has been reported that cancer [33], graft transplants [34], stroke [35] as well as non-disease settings, such as pregnancy [36,37], can lead to more pronounced fragmentation of cfDNA. In the cancer context, this fragmentation can shorten cfDNA, compared to healthy controls, in both total cfDNA pool [38][39][40] and in tumour-specific fragments, from �100 bp down to 57-85 bp [32,[41][42][43].…”

Cell-free nucleic acid patterns in disease prediction and monitoring—hype or hope?

“…Indeed, the cfDNA concentration correlates well with the severity at admission and with individual outcomes in IS patients [ 81 ] supporting meaningful measurements of plasma nuclear and mitochondrial cfDNA patterns [ 82 ] including specificity of the DNA fragmentation (300–400 bp range) profiling for diagnostic and prognostic purposes [ 77 , 81 – 83 ].…”

“…Some studies analysed cfDNA [ 66 – 69 ] as well as circulating miRNA panels (miR-192; -193b; -126; -130b; -221; -222) [ 70 – 72 ] after acute and chronic exercise. Last but not least circulating miRNA (miR-223; -21-5p; -30a-5p; -221-3p; -382-5p; -122-5p; -211-5p; PC-3p-57,664; PC-5p-12,969) [ 80 , 84 – 86 ], cfDNA and mtDNA could act as promising diagnostic and prognostic biomarkers of ischemic stroke [ 77 , 81 – 83 ].…”

Cell-Free DNA in the Pathogenesis and Therapy of Non-Infectious Inflammations and Tumors

“…In cases of stroke, the dynamically determined blood levels of cfDNA appear to be a valid and reliable option for establishing prognostic and diagnostic criteria [ 91 ]. While cfDNA has performed well in a number of studies as a stroke biomarker [ 92 , 93 ], none of the so-called stroke biomarkers identified to date have proven useful in medical practice, and there is still a long way to go before its clinical application, either as a standalone marker or as part of a biomarker panel.…”