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Editorial: Liquid biopsy in oncology: opportunity and challenges
Editorial29 July 2024
Editorial: Liquid biopsy in oncology: opportunity and challenges

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.

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BRIEF RESEARCH REPORT
22 January 2024
Early prognosis prediction in acute myeloid and acute lymphoid leukemia patients using cell-free DNA concentration ratios
Noreen Grace George, 10 more and Aroonima Misra

4,011 views

6 citations

ORIGINAL RESEARCH
18 January 2024
Prognostic and predictive role of liquid biopsy in lung cancer patients
Tuncay Goksel, 14 more and Yasemin Basbinar

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6 citations

ORIGINAL RESEARCH
30 November 2023
Validation of potential RNA biomarkers for prostate cancer diagnosis and monitoring in plasma and urinary extracellular vesicles
Agnese Brokāne, 7 more and Aija Linē
Validation of potential RNA biomarkers for prostate cancer diagnosis and monitoring in plasma and urinary extracellular vesicles
Prostate cancer (PCa), one of the most prevalent malignancies affecting men worldwide, presents significant challenges in terms of early detection, risk stratification, and active surveillance. In recent years, liquid biopsies have emerged as a promising non-invasive approach to complement or even replace traditional tissue biopsies. Extracellular vesicles (EVs), nanosized membranous structures released by various cells into body fluids, have gained substantial attention as a source of cancer biomarkers due to their ability to encapsulate and transport a wide range of biological molecules, including RNA. In this study, we aimed to validate 15 potential RNA biomarkers, identified in a previous EV RNA sequencing study, using droplet digital PCR. Initially, we tested the candidate biomarkers in plasma and urinary EVs collected before and after radical prostatectomy from 30 PCa patients and evaluated their diagnostic potential in a test cohort consisting of 20 benign prostate hyperplasia (BPH) and 20 PCa patients' plasma and urinary EVs. Next, we further validated our results in an independent cohort of plasma EVs from 31 PCa and 31 BPH patient. We found that the levels of NKX3-1 (p = 0.0008) in plasma EVs, and tRF-Phe-GAA-3b (p < 0.0001) tRF-Lys-CTT-5c (p < 0.0327), piR-28004 (p = 0.0081) and miR-375-3p (p < 0.0001) in urinary EVs significantly decreased after radical prostatectomy suggesting that the main tissue source of these RNAs is prostate and/or PCa. Two mRNA biomarkers -GLO1 and NKX3-1 showed promising diagnostic potential in distinguishing between PCa and BPH with AUC of 0.68 and 0.82, respectively in the test cohort and AUC of 0.73 and 0.65, respectively, in the validation cohort, when tested in plasma EVs. Combining these markers in a biomarker model yielded AUC of 0.85 and 0.71 in the test and validation cohorts, respectively. Although the PSA levels in blood could not distinguish PCa from BPH in our cohort, adding PSA to the mRNA biomarker model increased AUC from 0.71 to 0.76. This finding highlights the complementary nature of GLO1, NKX3-1, and PSA as combined biomarkers in liquid biopsies of PCa.

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14 citations

Brain tumours (PBT) are one of the most common malignancies during childhood, with variable severity according to the location and histological type. Certain types of gliomas, such a glioblastoma and diffuse intrinsic pontine glioma (DIPG), have a much higher mortality than ependymoma and medulloblastoma. Early detection of PBT is essential for diagnosis and therapeutic interventions. Liquid biopsies have been demonstrated using cerebrospinal fluid (CSF), mostly restricted to cell free DNA, which display limitations of quantity and integrity. In this pilot study, we sought to demonstrate the detectability and robustness of cell free histones in the CSF. We collected CSF samples from a pilot cohort of 8 children with brain tumours including DIPG, medulloblastoma, glioblastoma, ependymoma and others. As controls, we collected CSF samples from 9 children with unrelated blood malignancies and without brain tumours. We applied a multi-channel flow imaging approach on ImageStream(X) to image indiviual histone or histone complexes on different channels. Single histones (H2A, macroH2A1.1, macroH2A1.2 H2B, H3, H4 and histone H3 bearing the H3K27M mutation), and histone complexes are specifically detectable in the CSF of PBT patients. H2A and its variants macroH2A1.1/macroH2A1/2 displayed the strongest signal and abundance, together with disease associated H3K27M. In contrast, mostly H4 is detectable in the CSF of pediatric patients with blood malignancies. In conclusion, free histones and histone complexes are detectable with a strong signal in the CSF of children affected by brain tumours, using ImageStream(X) technology and may provide additive diagnostic and predictive information.

3,800 views

13 citations