Journal of Circulating Biomarkers

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ISSN / EISSN : 1849-4544 / 1849-4544
Published by: Aboutscience Srl (10.33393)
Total articles ≅ 87
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Carmen Luz Pessuti, Deise Fialho Costa, Kleber S. Ribeiro, , Thupten Tsering, , , Allexya Affonso Antunes Marcos, , , et al.
Journal of Circulating Biomarkers, Volume 11, pp 36-47; https://doi.org/10.33393/jcb.2022.2370

Abstract:
Purpose: Uveal melanoma (UM) is the most common intraocular malignant tumor in adults. Extracellular vesicles (EVs) have been extensively studied as a biomarker to monitor disease in patients. The study of new biomarkers in melanoma patients could prevent metastasis by earlier diagnosis. In this study, we determined the proteomic profile of EVs isolated from aqueous humor (AH), vitreous humor (VH), and plasma from UM patients in comparison with cancer-free control patients. Methods: AH, VH and plasma were collected from seven patients with UM after enucleation; AH and plasma were collected from seven cancer-free patients with cataract (CAT; control group). EVs were isolated using the membrane-based affinity binding column method. Nanoparticle tracking analysis (NTA) was performed to determine the size and concentration of EVs. EV markers, CD63 and TSG101, were assessed by immunoblotting, and the EV proteome was characterized by mass spectrometry. Results: Mean EV concentration was higher in all analytes of UM patients compared to those in the CAT group. In the UM cohort, the mean concentration of EVs was significantly lower in AH and plasma than in VH. In contrast, the mean size and size distribution of EVs was invariably identical in all analyzed analytes and in both studied groups (UM vs. CAT). Mass spectrometry analyses from the different analytes from UM patients showed the presence of EV markers. Conclusion: EVs isolated from AH, VH, and plasma from patients with UM showed consistent profiles and support the use of blood to monitor UM patients as a noninvasive liquid biopsy.
Stefan Erfurt, Meike Hoffmeister, Stefanie Oess, Katharina Asmus, Susann Patschan, Oliver Ritter,
Journal of Circulating Biomarkers, Volume 11, pp 28-35; https://doi.org/10.33393/jcb.2022.2386

Abstract:
Introduction: The prediction of acute kidney injury (AKI)-related outcomes remains challenging. Herein we prospectively quantified soluble ST2 (sST2), the circulating isoform of the IL-33 receptor, in hospitalized patients with AKI. Methods: In-hospital subjects with AKI of various etiology were identified through the in-hospital AKI alert system of the Brandenburg University hospital. sST2 was measured within a maximum of 48 hours from the time of diagnosis of AKI. The following endpoints were defined: in-hospital death, dialysis, recovery of kidney function until demission. Results: In total, 151 individuals were included in the study. The in-hospital mortality was 16.6%, dialysis therapy became mandatory in 39.7%, no recovery of kidney function occurred in 27.8%. sST2 was significantly higher in nonsurvivors (p = 0.024) but did not differ in the two other endpoints. The level of sST2 increased significantly with the severity of AKI. Further differences were detected in subjects with heart insufficiency (lower sST2), and in patients that required ICU treatment, or ventilatory therapy, or vasopressors (all higher). Conclusions: The current study suggests sST2 as biomarker of “acute distress”: it predicts post-AKI survival and substantially increases in subjects with a higher degree of cumulative morbidity under acute circumstances (e.g., ICU therapy, vasopressor administration).
, Agnes Tello, Petra Rauchhaus, Virginia Hernandez Santiago, Fergus Daly
Journal of Circulating Biomarkers, Volume 11, pp 24-27; https://doi.org/10.33393/jcb.2022.2337

Abstract:
Background: Patients with more severe forms of SARS-CoV-2 exhibit activation of immunological cascades. Participants (current or ex-smokers with at least 20 years pack history) in a trial (Early Diagnosis of Lung Cancer, Scotland [ECLS]) of autoantibody detection to predict lung cancer risk had seven autoantibodies measured 5 years before the pandemic. This study compared the response to Covid infection in study participants who tested positive and negative to antibodies to tumour-associated antigens: p53, NY-ESO-1, CAGE, GBU4-5, HuD, MAGE A4 and SOX2. Methods: Autoantibody data from the ECLS study was deterministically linked to the EAVE II database, a national, real-time prospective cohort using Scotland’s health data infrastructure, to describe the epidemiology of SARS-CoV-2 infection, patterns of healthcare use and outcomes. The strength of associations was explored using a network algorithm for exact contingency table significance testing by permutation. Results: There were no significant differences discerned between SARS-CoV-2 test results and EarlyCDT-Lung test results (p = 0.734). An additional analysis of intensive care unit (ICU) admissions detected no significant differences between those who tested positive and negative. Subgroup analyses showed no difference in COVID-19 positivity or death rates amongst those diagnosed with chronic obstructive pulmonary disease (COPD) with positive and negative EarlyCDT results. Conclusions: This hypothesis-generating study demonstrated no clinically valuable or statistically significant associations between EarlyCDT positivity in 2013-15 and the likelihood of SARS-CoV-2 positivity in 2020, ICU admission or death in all participants (current or ex-smokers with at least 20 years pack history) or in those with COPD or lung cancer.
Jonas Holdmann, , Claudia Klinger, Michael Kaufmann, , , , Stephan Degener, , Stephan Roth, et al.
Published: 10 February 2022
Journal of Circulating Biomarkers, Volume 11, pp 5-13; https://doi.org/10.33393/jcb.2022.2317

Abstract:
Introduction: Prostate cancer (PCa) is the second most frequently diagnosed cancer and the fifth most cancer-related cause of death worldwide. Various tools are used in the diagnosis of PCa, such as the Prostate-Specific Antigen (PSA) value or digital rectal examination. A final differentiation from benign prostate diseases such as benign prostatic hyperplasia (BPH) can often only be made by a transrectal prostate biopsy. This procedure carries post-procedural complications for the patients and may lead to hospitalization. Urinary exosomes contain unique components, such as microRNAs (miRNAs) with information about their original tissue. As miRNAs appear to play a role in the development of PCa, they might be useful to develop procedures that could potentially make transrectal biopsies avoidable in certain situations. Methods: The current study aimed to investigate whether miRNAs from urinary exosomes can be used to differentiate PCa from BPH. For this purpose, urine samples from 28 patients with PCa and 25 patients with BPH were collected and analysed using next-generation sequencing to obtain expression profiles. Results and conclusion: The two miRNAs hsa-miR-532-3p and hsa-miR-6749-5p showed a significant differential expression within the group of patients with PCa in a training subset of the data containing 32 patients. They were further validated on the independent test data subset containing 20 patients. Additionally, a machine learning algorithm was used to generate a miRNA pattern to distinguish the two disease entities. Both approaches seem to be suitable for the search of alternative diagnostic tools for the differentiation of benign and malignant prostate diseases.
Luisa Albanese, Gemma Caliendo, Giovanna D'Elia, Luana Passariello, Anna Maria Molinari, Claudio Napoli, Maria Teresa Vietri
Journal of Circulating Biomarkers, Volume 11, pp 1-4; https://doi.org/10.33393/jcb.2022.2328

Abstract:
Our data confirm that intact fibroblast growth factor 23 (iFGF-23) concentration is increased in patients with chronic kidney disease (CKD) and that it increases with disease progression (stages I-V). Therefore, iFGF-23 could be considered an early biomarker in the course of chronic kidney disease-mineral bone disorder (CKD-MBD), which has several aspects that make it potentially useful in clinical practice. The availability of an automated method for iFGF-23 assay may represent an added value in the management of the patient with CKD-MBD already from the early stages of the disease, before the increase of the routinely used laboratory parameters, 1-84 parathyroid hormone (PTH) and 25-OH-vitamin D (25-OH-vitD), which occur in more advanced stages of the disease.
Frank M. Balis, Cynthia Lester McCully, Christine M. Busch, , Katherine E. Warren
Journal of Circulating Biomarkers, Volume 10, pp 26-29; https://doi.org/10.33393/jcb.2021.2329

Abstract:
Background: The ganglioside GD2 is a potential circulating tumor biomarker for the childhood cancer, neuroblastoma. Interpreting the levels of a circulating tumor biomarker depends in part on a knowledge of the biomarker’s clinical pharmacology. Background: The ganglioside GD2 is a potential circulating tumor biomarker for the childhood cancer neuroblastoma. Interpreting the levels of a circulating tumor biomarker depends in part on a knowledge of the biomarker’s clinical pharmacology. Methods: We studied the plasma and cerebrospinal fluid (CSF) pharmacokinetics of the C18 lipoform of GD2 in two nonhuman primates with indwelling subcutaneous CSF lateral ventricular reservoir systems. GD2 was quantified with a validated high-performance liquid chromatography (HPLC)/tandem mass spectrometry assay. GD2 was administered as a short intravenous infusion and frequent plasma and CSF samples were drawn over 72 hours. Results: GD2 plasma concentration declined monoexponentially with a half-life of 16 hours. Clearance was 0.0136 and 0.0131 L/h and volume of distribution (Vd) was 0.035 and 0.038 L/kg in the two animals. Vd was equivalent to plasma volume. Greater than 98% of GD2 in plasma is in a bound form consistent with its known association with lipoproteins and accounting for its limited volume of distribution. GD2 did not cross over from plasma into the CSF. Conclusions: The pharmacokinetic profile of GD2 is favorable for a circulating tumor biomarker. This study demonstrates the value of characterizing the clinical pharmacology of circulating biomarkers to better understand their clinical behavior.
Stefan Erfurt, Meike Hoffmeister, Stefanie Oess, Katharina Asmus, Oliver Ritter, ,
Published: 30 November 2021
Journal of Circulating Biomarkers, Volume 10, pp 20-25; https://doi.org/10.33393/jcb.2021.2327

Abstract:
Interleukin-33 (IL-33), a member of the IL-1 family, is critically involved in the modulation of the activity of a diverse range of immunocompetent cells. Essential roles have been implicated in cardioprotection, in both innate and adaptive immune responses in mucosal organs, and in the maintenance of adipose tissue cells. Over the past 10 years, several studies evaluated the usability of IL-33 as a biomarker in diseases of inflammatory and noninflammatory origin. Our group is currently evaluating the predictive role of serum IL-33 in acute kidney injury (AKI). The aim of the article is to discuss selected studies on IL-33 in different diseases and its potential role as a biomarker molecule.
Stefan Schreier, Prapaphan Budchart, Suparerk Borwornpinyo, Wichit Arpornwirat, Wannapong Triampo
Journal of Circulating Biomarkers, Volume 10, pp 14-19; https://doi.org/10.33393/jcb.2021.2220

Abstract:
Background: The circulating rare cell population is diverse and rich in diagnostic information. Its characterization and clinical exploitation by cell-based liquid biopsy is an ongoing research task. Bone marrow is one of the major contributors to the peripheral blood rare cell population and, consequently, determines individual rare cell profiles thus depending on bone marrow health status. Bone marrow damage has been associated with aggressive or late-stage systemic diseases and egress of various bone marrow cells into the blood circulation. The association of quantity and heterogeneity of circulating erythroblast with bone marrow damage is of particular interest. Methods: Circulating CD71high/CD45-/Hoechsthigh blast cells from healthy, noncancer- and cancer-afflicted donors were enriched by CD45 depletion and analyzed by immunofluorescence microscopy. Results: A new finding of aberrant and mitotic circulating erythroid-like cells that appear similar across blood donors afflicted with various systemic pathologies is reported. Further presented is a classification of said erythroblast-like cells in nine subcategories according to morphological differences between phenotypically similar cells. Conclusion: Aberrant and mitotic bone marrow-derived rare circulating erythroid-like cells can be detected in the blood of afflicted individuals but not in healthy donors, suggesting the cause of bone marrow damage.
Vittoria Barchiesi, Vittorio Simeon, Claudia Sandomenico, Monica Cantile, Dionigio Cerasuolo, Paolo Chiodini, Alessandro Morabito,
Journal of Circulating Biomarkers, Volume 10, pp 9-13; https://doi.org/10.33393/jcb.2021.2212

Abstract:
Introduction: Progastrin-releasing peptide (proGRP), a precursor of GRP, has been recently reported as a putative circulating biomarker for differential diagnosis between non–small cell lung cancer (NSCLC) and SCLC. We evaluated the diagnostic effectiveness of proGRP to differentiate patients with NSCLC and SCLC and the usefulness of combined measurement of proGRP and neuron-specific enolase (NSE) for diagnosing SCLC. Methods: Serum proGRP, NSE, cytokeratin 19 fragment 21-1 (CYFRA 21.1), squamous cell carcinoma antigen (SCC Ag) and carcinoembryonic antigen (CEA) were prospectively collected and measured in patients with a new diagnosis of lung cancer. Serum proGRP was also measured in healthy subjects. The serum proGRP, NSE, CYFRA 21.1 and CEA concentrations were determined by an electrochemiluminescence immunoassay and the serum SCC Ag concentration was determined by an automated immunofluorescence assay. Differences between proGRP and NSE in patients with SCLC and NSCLC were evaluated and compared using Mann-Whitney test. Results: A total of 77 patients affected by SCLC (n = 17) and NSCLC (n = 60) were enrolled in the present study. Moreover, 50 cases of healthy subjects were analyzed for proGRP. SCLC patients showed a significantly higher proGRP (1,484 pg/mL; range 168-3,777) levels compared to NSCLC patients (45 pg/mL; range 31.7-60.6), p<0.0001. In healthy subjects the median proGRP level was 36.1 (28.8-43.5) pg/mL, significantly lower than SCLC patients. ProGRP showed a higher specificity when compared to NSE, with a difference in proportion of 47.5% (95% confidence interval 32.5% to 62.5%, p<0.001). Serial measurements of proGRP in SCLC patients showed a decrease in responsive chemotherapy patients.
Laura Macías-Muñoz, Robin Wijngaard, Bernardino González-De la Presa, Jose Luis Bedini, , Wladimiro Jiménez
Journal of Circulating Biomarkers, Volume 10, pp 1-8; https://doi.org/10.33393/jcb.2021.2194

Abstract:
Background: COVID-19 causes high mortality and long hospitalization periods. The aim of this study was to search for new early prognostic strategies accessible to most health care centers. Methods: Laboratory results, demographic and clinical data from 500 patients with positive SARS-CoV-2 infection were included in our study. The data set was split into training and test set prior to generating different multivariate models considering the occurrence of death as the response variable. A final computational method called the BGM score was obtained by combining the previous models and is available as an interactive web application. Results: The logistic regression model comprising age, creatinine (CREA), D-dimer (DD), C-reactive protein (CRP), platelet count (PLT), and troponin I (TNI) showed a sensitivity of 47.3%, a specificity of 98.7%, a kappa of 0.56, and a balanced accuracy of 0.73. The CART classification tree yielded TNI, age, DD, and CRP as the most potent early predictors of mortality (sensitivity = 68.4%, specificity = 92.5%, kappa = 0.61, and balanced accuracy = 0.80). The artificial neural network including age, CREA, DD, CRP, PLT, and TNI yielded a sensitivity of 66.7%, a specificity of 92.3%, a kappa of 0.54, and a balanced accuracy of 0.79. Finally, the BGM score surpassed the prediction accuracy performance of the independent multivariate models, yielding a sensitivity of 73.7%, a specificity of 96.5%, a kappa of 0.74, and a balanced accuracy of 0.85. Conclusions: The BGM score may support clinicians in managing COVID-19 patients and providing focused interventions to those with an increased risk of mortality.
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