Circulating nucleic acids in plasma and serum (CNAPS): applications in oncology

Abstract

The presence of small amounts of circulating nucleic acids in plasma and serum (CNAPS) is not a new finding. The verification that such amounts are significantly increased in cancer patients, and that CNAPS might carry a variety of genetic and epigenetic alterations related to cancer development and progression, has aroused great interest in the scientific community in the last decades. Such alterations potentially reflect changes that occur during carcinogenesis, and include DNA mutations, loss of heterozygosity, viral genomic integration, disruption of microRNA, hypermethylation of tumor suppressor genes, and changes in the mitochondrial DNA. These findings have led to many efforts toward the implementation of new clinical biomarkers based on CNAPS analysis. In the present article, we review the main findings related to the utility of CNAPS analysis for early diagnosis, prognosis, and monitoring of cancer, most of which appear promising. However, due to the lack of harmonization of laboratory techniques, the heterogeneity of disease progression, and the small number of recruited patients in most of those studies, there has been a poor translation of basic research into clinical practice. In addition, many aspects remain unknown, such as the release mechanisms of cell-free nucleic acids, their biological function, and the way by which they circulate in the bloodstream. It is therefore expected that in the coming years, an improved understanding of the relationship between CNAPS and the molecular biology of cancer will lead to better diagnosis, management, and treatment.

The effect of exercise on skeletal muscle glucose uptake in type 2 diabetes: An epigenetic perspective

“…So far >900 miRNAs have been discovered [28]. The mature miRNA with 20-24 nucleotides (nt) are produced from ~70 nt precursor RNA originated from long 300-5,000 base pair primary RNA.…”

Further the liquid biopsy: Gathering pieces of the puzzle of genometastasis theory

“…The effectiveness of this approach has been demonstrated in different malignancies including breast, pancreatic and colorectal cancer (CRC)[1]. In the case of pancreatic cancer, liquid biopsy provides an advantageous technology regarding the anatomical and clinical difficulties for pancreatic tissue[2].…”

“…It can be present in circulation in both protein-associated and free form[34]. Circulating mitDNA measurement and mutation analysis has been proposed to diagnose different malignancies such as breast tumors or epithelial ovarian cancer and hepatocellular or colorectal cancer, respectively[1,36]. …”

“…Apart from the clinical discussion (which has not been finished yet), the fact was that circulation of tumor cells appeared to have lesser value than attributed. In parallel, the evidence of high levels of cell-free nucleic acids in plasma of cancer patients and tumor-bearing animals led us to examine the biological role of such molecules[1,29,71]. Firstly in cancer models using immunocompetent animals and later in clinical studies with colon cancer patients, we demonstrated the biological feasibility of gene transfer and of the transformation of cells by cell-free tumor-derived nucleic acids in the plasma[41,72,73].…”

The Early Diagnosis in Lung Cancer by the Detection of Circulating Tumor DNA

“…The cfDNA in the plasma of cancer patients has been believed to contain circulating tumor DNA (ctDNA) for decades, although over ninety percent of cfDNA in healthy individuals is from metabolism of normal blood cells. Previous studies suggested that cfDNA can serve as a sensitive tool for early diagnosis of cancers [6][7][8][9][10] and the levels of ctDNA were reported to increase with the severity of cancers 11,12 . Currently, ctDNA is gradually recognized as a significant biomarker for cancer monitoring and treatment 3,5 , especially after several research groups reported the positive detection of ctDNA in early-stagy cancers [13][14][15][16] .…”