
The early detection and classification of pediatric brain tumors (PBT) are critical for effective treatment. Identifying and monitoring molecular markers improves pediatric tumors' clinical management and can serve as companion diagnostic tools to magnetic resonance imaging (MRI) and histology. Towards this, cfDNA in cerebrospinal fluid (CSF) has been a focus in several studies as a minimally invasive method for diagnosing and monitoring brain tumors. However, the utility of CSF cfDNA is limited due to its quantity and integrity. Histones have been previously identified as potential diagnostic tools in various adult cancers, but not in PBT.Using ImageStream(x) technology, Buzova et al explored the potential of cell-free histones in CSF as an alternative biomarker for the diagnosis of PBT. The study found that single histones (H2A, macroH2A1.1, macroH2A1.2, H2B, H3, H4) and histone complexes are detectable in the CSF of patients with brain tumors. These histones could provide valuable diagnostic and prognostic information, complementing existing MRI and histological analysis methods (Buzova et al. 2023).Prostate cancer (PCa) is one of the most common fatal malignancy. Traditional diagnostic methods, such as PSA tests and histopathology of transrectal ultrasound scan (TRUS)-guided biopsies, have limitations in specificity and risk of infection at puncture sites. Extracellular vesicles (EVs) in body fluids, have emerged as promising non-invasive tools for cancer diagnostics. Brokāne et al focused on identifying and validating RNA biomarkers in plasma and urine EVs for prostate cancer diagnosis and monitoring. In their study, authors have validated 15 potential RNA biomarkers, identified from previous EV RNA sequencing studies from PCa patients before and after radical prostatectomy. The diagnostic potential of these biomarkers was evaluated in a test cohort and validated in an independent cohort of plasma EVs. Authors showed the significant decrease in specific RNA biomarkers (NKX3-1, tRF-Phe-GAA-3b, tRF-Lys- CTT-5c, piR-28004, miR-375-3p) in urinary EVs after prostatectomy, suggesting their association with PCa. NKX3-1 and GLO1 mRNA biomarkers notably showed promising diagnostic potential in distinguishing PCa from BPH. Combining these biomarkers with PSA improved the diagnostic accuracy for PCa (Brokāne et al. 2023).A study by George et al investigates the potential of cfDNA as a biomarker for predicting outcomes in patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). The study aimed to establish a cfDNA ratio cut-off value for risk stratification and minimal residual disease (MRD) prediction. The ratio of cfDNA reduction from baseline to the end of induction was a strong predictor of poor outcomes in high-risk patients, regardless of MRD status. A cfDNA ratio score of 2.6 or higher predicted poor outcomes with greater accuracy than conventional MRD detection by flow cytometry. A higher cfDNA ratio at diagnosis/remission or baseline indicates poor prognosis. The study suggested that cfDNA ratio scoring could be a valuable tool for prognosis in acute leukemia patients (George et al. 2023).While the studies published in this special issue demonstrate the potential of liquid biopsy for cancer detection, the studies utilized small sample sizes; further research for validating biomarkers in more extensive and diverse cohorts is warranted. In addition, most of the studies focussed on the need to explore the combinatorial use of nucleotide, protein, and metabolite to form the basis of better diagnosis/prognosis tools. The findings support the integration of liquid biopsy into routine clinical practice for personalized cancer management. Combining liquid biopsy with other diagnostic methods may enhance cancer detection and management's overall accuracy and reliability.

