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Circulating Cell-Free Nucleic Acids and Cancers: 3rd Edition

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: 30 December 2025 | Viewed by 306

Special Issue Editor


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Guest Editor
Department of Life Sciences, University of Trieste, Giorgeri 1, 34127 Trieste, Italy
Interests: biological fluids; cancer; cancer biomarkers; cfDI; cfDNA; cfNA; copy number variation; ctDNA; ddPCR; disease-free survival; epigenetic; epigenetic sequencing; exosome; extracellular vesicle; genotyping; liquid biopsy; miRNA; mRNA; mutation; ncRNA; next- generation sequencing; overall survival; progression-free survival; recurrence-free survival; whole-exome sequencing
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Special Issue Information

Dear Colleagues,

This Special Issue is a continuation of our previous Special Issue, “Circulating Cell-Free Nucleic Acids and Cancers: 2nd Edition”. Improvements in the molecular diagnosis and prognosis of cancer and better evaluation of therapeutic intervention are urgently needed to offer more personalized treatment to patients.

In this respect, liquid biopsy shows great potential in precision medicine, especially for solid tumors. It is applicable for screening, diagnosis, prognosis, and for predictive value and monitoring of the disease. Liquid biopsy is a versatile and minimally invasive procedure, and the availability of high-throughput technologies allows for the analysis of very small quantities of targets.

In liquid biopsy, targeting circulating cell-free nucleic acid (cfNA) is one of the most interesting aspects because many cancer biomarkers, already identified in the tissue, can be found in circulating cell-free DNA (cfDNA). In cfDNA, a fraction of tumor DNA (ctDNA) can be searched by identifying both the cancer-related mutations and the copy number variation of specific genes. The cancer-related methylation status of selected genes in cfDNA can also be measured. Moreover, it has been demonstrated that ctDNA quantity can be related to the integrity index of the cfDNA, (cfDI), i.e., the fraction of long over short-nested fragments of the same DNA target. Many studies indicate that ctDNA analysis can depict tumor heterogeneity. Recently, the role of circulating-free RNA molecules (cfRNA) in diagnosis, prognosis, and therapy responsiveness is emerging. In general, studies on cfNA have a high translational potential for clinical practice, as in EGFR mutations validated by FDA in 2016 for NSCLC. Finally, the analysis of cfNA has the advantage of being highly specific but simpler and lower costing than analyses using circulating tumor cells. Thus, they can be useful to facilitate therapeutic decision making and to predict tumor burden after therapies or the acquired treatment resistance.

Topics of interest for this Special Issue include, but are not limited to, the following:

  • Liquid biopsy targeting cfNA for cancer molecular diagnostics;
  • Clinical validity and utility of cfNA analysis for tumors;
  • Epigenetic markers for cancer by liquid biopsy;
  • Extracellular vesicle biomarkers in liquid biopsy;
  • New insights in cfNA biomarkers (cfDNA, ctDNA, cfDI and cfRNA) for the screening, diagnosis, prognosis, follow-up, and therapeutic management of tumors;
  • New techniques to evaluate cfNA;
  • Liquid biopsy on exosome for cancer diagnostics.

Dr. Bruna Scaggiante
Guest Editor

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Keywords

  • biological fluids
  • cancer
  • cancer biomarkers
  • cfDI
  • cfDNA
  • cfNA
  • copy number variation
  • ctDNA
  • ddPCR
  • disease-free survival
  • epigenetic
  • epigenetic sequencing
  • exosome
  • extracellular vesicle
  • genotyping
  • liquid biopsy
  • miRNA
  • mRNA
  • mutation
  • ncRNA
  • next-generation sequencing
  • overall survival
  • progression-free survival
  • recurrence-free survival
  • whole-exome sequencing

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Published Papers (1 paper)

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Research

15 pages, 942 KB  
Article
LINE-1 266/97 and ALU 260/111 Copy Number Ratios in Circulating Cell-Free DNA in Plasma as Potential Biomarkers for the Detection of Prostate Cancer: A Pilot Case-Control Study
by Domenico Tierno, Nicola Pavan, Fabiola Giudici, Gabriele Grassi, Eleonora Valeri, Fabrizio Zanconati, Fabio Traunero, Giovanni Liguori and Bruna Scaggiante
Int. J. Mol. Sci. 2025, 26(18), 8862; https://doi.org/10.3390/ijms26188862 - 11 Sep 2025
Viewed by 191
Abstract
Prostate cancer (PCa) is the second most common cancer and the fourth leading cause of cancer death in men worldwide. PSA screening for PCa diagnosis is not disease-specific; the discovery of novel and efficient biomarkers is therefore recommended. The concentration and integrity of [...] Read more.
Prostate cancer (PCa) is the second most common cancer and the fourth leading cause of cancer death in men worldwide. PSA screening for PCa diagnosis is not disease-specific; the discovery of novel and efficient biomarkers is therefore recommended. The concentration and integrity of circulating cell-free DNA (ccfDNA) in the blood of PCa patients could represent innovative and more specific tools for the clinical management of PCa. Digital droplet PCR (ddPCR) was used to determine the copy number ratio of ALU 260/111 bp and LINE-1 266/97 bp in the plasma of a cohort of 40 PCa and 18 BPH patients in a blinded prospective study. The amount of ccfDNA in the plasma of PCa and BPH patients was calculated from the EEF1A2 and ESR1 gene copy numbers. The ALU 260/111 and LINE-1 266/97 copy number ratios were significantly lower in the plasma of PCa patients compared to benign prostatic hyperplasia (BPH) ones (p-value; ALU 260/111: 0.006; LINE-1 266/97: 0.037). The area under the curve (AUC) indicated a good accuracy of two ratios and their product (ALU 260/111 * LINE 266/97, A*L) in discriminating PCa patients from BPH ones (AUC; ALU 260/111: 0.72; LINE-1 266/97: 0.67; A*L: 0.76). The ccfDNA concentration measured by EEF1A2 and ESR1 targets was significantly higher in the plasma of PCa patients compared to BPH patients, (p-value: EEF1A2, 0.017; ESR1, 0.024). The pilot ddPCR analysis of the ALU 260/111 and LINE-1 266/97 ratios in plasma indicates a new, reproducible and specific method for improving the early diagnosis of PCa. Further studies on larger cohorts are needed to confirm the results and clinical application. Full article
(This article belongs to the Special Issue Circulating Cell-Free Nucleic Acids and Cancers: 3rd Edition)
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