Biomarker Insights[JOURNAL]
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200 papers
Glycerophosphoinositol is Elevated in Blood Samples From pigs, Mice, and CLN3-Affected Individuals.
Brudvig JJ, Swier VJ, Johnson TB … +7 more , Cain JC, Pratt M, Rechtzigel M, Leppert H, Dang Do AN, Porter FD, Weimer JM
Biomark Insights · 2022 · PMID 36212622 · Full text
INTRODUCTION: CLN3 Batten disease is a rare pediatric neurodegenerative lysosomal disorder caused by biallelic disease-associated variants in Despite decades of intense research, specific biofluid biomarkers of disease...
INTRODUCTION: CLN3 Batten disease is a rare pediatric neurodegenerative lysosomal disorder caused by biallelic disease-associated variants in Despite decades of intense research, specific biofluid biomarkers of disease status have not been reported, hindering clinical development of therapies. Thus, we sought to determine whether individuals with CLN3 Batten disease have elevated levels of specific metabolites in blood. METHODS: We performed an exhaustive metabolomic screen using serum samples from a novel minipig model of CLN3 Batten disease and validated findings in pig serum and CSF and mouse serum. We further validate biomarker candidates with a retrospective analysis of plasma and CSF samples collected from participants in a natural history study. Plasma samples were evaluated from 22 phenotyped individuals with CLN3 disease, 15 heterozygous carriers, and 6 non-affected non-carriers (NANC). RESULTS: CLN3 pig serum samples from 4 ages exhibited large elevations in 4 glycerophosphodiester species: glycerophosphoinositol (GPI), glycerophosphoethanolamine (GPE), glycerophosphocholine (GPC), and glycerophosphoserine (GPS). GPI and GPE exhibited the largest elevations, with similar elevations found in pig CSF and mouse serum. In plasma samples from individuals with CLN3 disease, glycerophosphoethanolamine and glycerophosphoinositol were significantly elevated with glycerophosphoinositol exhibiting the clearest separation (mean 0.1338 vs 0.04401 nmol/mL for non-affected non-carriers). Glycerophosphoinositol demonstrated excellent sensitivity and specificity as a biomarker, with a receiver operating characteristic area under the curve of 0.9848 ( = .0003). CONCLUSIONS: GPE and GPI could have utility as biomarkers of CLN3 disease status. GPI, in particular, shows consistent elevations across a diverse cohort of individuals with CLN3. This raises the potential to use these biomarkers as a blood-based diagnostic test or as an efficacy measure for disease-modifying therapies.
Serum ACE2 Level is Associated With Severe SARS-CoV-2 Infection: A Cross-Sectional Observational Study.
Bani Hani A, Abu Tarboush N, Bani Ali M … +8 more , Alabhoul F, Alansari F, Abuhani A, Al-Kawak M, Shamoun B, Albdour S, Abu Abeeleh M, Ahram M
Biomark Insights · 2022 · PMID 36156891 · Full text
OBJECTIVES: Angiotensin-converting enzyme 2 (ACE2) represents the primary receptor for SARS-CoV-2 to enter endothelial cells, causing coronavirus disease of 2019 (COVID-19). In this study, we investigate the association...
OBJECTIVES: Angiotensin-converting enzyme 2 (ACE2) represents the primary receptor for SARS-CoV-2 to enter endothelial cells, causing coronavirus disease of 2019 (COVID-19). In this study, we investigate the association between circulating ACE2 levels with the severity of COVID-19. METHODS: Serum ACE2 levels were measured in 144 COVID-19-positive subjects at hospital admission, and 123 COVID-19-negative control subjects. The association between ACE2 and clinical outcomes was analyzed. RESULTS: About 144 COVID-19 patients and 123 healthy controls data were analyzed, the mean age of patients was 62 years and 50% of them were males. The mean age of the control group was 55 years and 63% were males. ACE-II level was measured and compared between COVID-19 patients and controls and revealed no significant differences ( > .05). ACE-II level was measured in COVID-19 patients and compared between different patient's subgroups, ACE II level was not dependent on gender, smoking, ACE intake, or comorbidities ( > .05), and was significantly correlated with cardiovascular diseases (CVS) (-value = .046) ICU admission (-value = .0007) and Death (-value = .0082). CONCLUSION: There was no significant difference between the COVID-19 and Control group, however, ACE2 serum level was significantly higher in patients with COVID-19 who were critically ill or non-survivors, its increased level is also associated with length of stay. Elevated ACE2 level is associated with the severity of COVID-19 disease, and it has the potential to be a predictor of the severity of the disease.
Measuring Some Oxidative Stress Biomarkers in Autistic Syrian Children and Their Siblings: A Case-Control Study.
Nasrallah O, Alzeer S
Biomark Insights · 2022 · PMID 36120384 · Full text
OBJECTIVE: Autism Spectrum Disorder (ASD) is a common neurodevelopmental disorder whose cause remains unknown. Oxidative stress is one of the possible causes of many disorders, including neurological ones. This study aim...
OBJECTIVE: Autism Spectrum Disorder (ASD) is a common neurodevelopmental disorder whose cause remains unknown. Oxidative stress is one of the possible causes of many disorders, including neurological ones. This study aims to measure some oxidative stress biomarkers (Malondialdehyde "MDA," Advanced Oxidation Protein Product "AOPP," Glutathione "GSH") within Syrian children with ASD. METHODS: MDA, AOPP & GSH were measured in the plasma of a total of 60 children. The ages of the children ranged from 1 to 13 years old. Thirty children had ASD and were compared with 30 controls that don't have ASD. Fifteen of the controls were siblings of an ASD child, while the remaining 15 had no relations with ASD. RESULTS: MDA and AOPP plasma levels were higher in ASD children compared with non-related controls ( = .0001). However, there were no significant differences between MDA and AOPP plasma levels in ASD children in comparison with related controls ( > .05). Alternatively, GSH plasma levels were lower in ASD children compared with both related and non-related controls ( = .0001). CONCLUSION: Further studies are needed to investigate more regarding the diagnostic use of oxidative stress biomarkers, and the therapeutic use of antioxidants in children affected with the autism spectrum disorder.
High Levels of the Carcinogenic Tobacco-Specific Nitrosamine NNAL and Associated Findings in Children of Smokers: A Case Series.
Mahabee-Gittens EM, Matt GE, Merianos AL
Biomark Insights · 2022 · PMID 35982916 · Full text
High levels of NNAL, the tobacco smoke exposure (TSE) biomarker of the carcinogen 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), indicate future cancer risk. A prior study of smokers' children revealed NNAL levels...
High levels of NNAL, the tobacco smoke exposure (TSE) biomarker of the carcinogen 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), indicate future cancer risk. A prior study of smokers' children revealed NNAL levels as high as active smokers. Therefore, we conducted a case series to examine the sociodemographics, TSE and clinical patterns, and other TSE biomarker levels in 9 children with extreme NNAL levels of >200 pg/ml to generate hypotheses and explore potential causes and implications. We identified 0 to 4-year-olds who presented to an emergency setting and lived with ⩾1 smoker who were part of a parental tobacco cessation trial (n = 461). Of these children, 52 had urinary NNAL, cotinine, and N-oxides results (n = 52). Nine children (17.3%) had NNAL levels >200 pg/ml, ranging from 206.4 to 1399.0 pg/ml (Median (Mdn) = 489.2 pg/ml; Interquartile Range (IQR) = 222.7-1289.3 pg/ml). The cotinine Mdn (IQR) was 38.5 (10.3-102.2) ng/ml and the N-oxides Mdn (IQR) = 93.8 (24.7-109.6) pg/ml. While all biomarker levels were alarmingly high, these young children would not have been flagged for very high cancer risk based on urinary cotinine levels alone. This underscores the critical role of comprehensive TSE biomarker measurement in capturing different TSE exposure patterns and assessing children's future risk for cancer and other TSE-related morbidities.
Joint Modeling of Repeated Measurements of Different Biomarkers Predicts Mortality in COVID-19 Patients in the Intensive Care Unit.
Tong-Minh K, van der Does Y, van Rosmalen J … +5 more , Ramakers C, Gommers D, van Gorp E, Rizopoulos D, Endeman H
Biomark Insights · 2022 · PMID 35859926 · Full text
INTRODUCTION: Predicting disease severity is important for treatment decisions in patients with COVID-19 in the intensive care unit (ICU). Different biomarkers have been investigated in COVID-19 as predictor of mortality...
INTRODUCTION: Predicting disease severity is important for treatment decisions in patients with COVID-19 in the intensive care unit (ICU). Different biomarkers have been investigated in COVID-19 as predictor of mortality, including C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), and soluble urokinase-type plasminogen activator receptor (suPAR). Using repeated measurements in a prediction model may result in a more accurate risk prediction than the use of single point measurements. The goal of this study is to investigate the predictive value of trends in repeated measurements of CRP, PCT, IL-6, and suPAR on mortality in patients admitted to the ICU with COVID-19. METHODS: This was a retrospective single center cohort study. Patients were included if they tested positive for SARS-CoV-2 by PCR test and if IL-6, PCT, suPAR was measured during any of the ICU admission days. There were no exclusion criteria for this study. We used joint models to predict ICU-mortality. This analysis was done using the framework of joint models for longitudinal and survival data. The reported hazard ratios express the relative change in the risk of death resulting from a doubling or 20% increase of the biomarker's value in a day compared to no change in the same period. RESULTS: A total of 107 patients were included, of which 26 died during ICU admission. Adjusted for sex and age, a doubling in the next day in either levels of PCT, IL-6, and suPAR were significantly predictive of in-hospital mortality with HRs of 1.523 (1.012-6.540), 75.25 (1.116-6247), and 24.45 (1.696-1057) respectively. With a 20% increase in biomarker value in a subsequent day, the HR of PCT, IL-6, and suPAR were 1.117 (1.03-1.639), 3.116 (1.029-9.963), and 2.319 (1.149-6.243) respectively. CONCLUSION: Joint models for the analysis of repeated measurements of PCT, suPAR, and IL-6 are a useful method for predicting mortality in COVID-19 patients in the ICU. Patients with an increasing trend of biomarker levels in consecutive days are at increased risk for mortality.
Nephrotoxic Biomarkers with Specific Indications for Metallic Pollutants: Implications for Environmental Health.
Pócsi I, Dockrell ME, Price RG
Biomark Insights · 2022 · PMID 35859925 · Full text
Environmental and occupational exposure to heavy metals and metalloids is a major global health risk. The kidney is often a site of early damage. Nephrotoxicity is both a major consequence of heavy metal exposure and pot...
Environmental and occupational exposure to heavy metals and metalloids is a major global health risk. The kidney is often a site of early damage. Nephrotoxicity is both a major consequence of heavy metal exposure and potentially an early warning of greater damage. A paradigm shift occurred at the beginning of the 21st century in the field of renal medicine. The medical model of kidney failure and treatment began to give way to a social model of risk factors and prevention with important implications for environmental health. This development threw into focus the need for better biomarkers: markers of exposure to known nephrotoxins; markers of early damage for diagnosis and prevention; markers of disease development for intervention and choice of therapy. Constituents of electronic waste, e-waste or e-pollution, such as cadmium (Cd), lead (Pb), mercury (HG), arsenic (As) and silica (SiO) are all potential nephrotoxins; they target the renal proximal tubules through distinct pathways. Different nephrotoxic biomarkers offer the possibility of identifying exposure to individual pollutants. In this review, a selection of prominent urinary markers of tubule damage is considered as potential tools for identifying environmental exposure to some key metallic pollutants.
The Role of Biomarkers in Hospitalized COVID-19 Patients With Systemic Manifestations.
Schneider M
Biomark Insights · 2022 · PMID 35783222 · Full text
The following article aims to review COVID-19 biomarkers used in hospital practice. It is apparent that COVID-19 is not simply a pulmonary disease but has systemic manifestations. For this reason, biomarkers must be used...
The following article aims to review COVID-19 biomarkers used in hospital practice. It is apparent that COVID-19 is not simply a pulmonary disease but has systemic manifestations. For this reason, biomarkers must be used in the management of diagnosed patients to provide holistic care. Patients with COVID-19 have been shown to have pulmonary, hepatobiliary, cardiovascular, neurologic, and renal injury, along with coagulopathy and a distinct cytokine storm. Biomarkers can effectively inform clinicians of systemic organ injury due to COVID-19. Furthermore, biomarkers can be used in predictive models for severe COVID-19 in admitted patients. The utility of doing so is to allow for risk stratification and utilization of proper treatment protocols. In addition, COVID-19 biomarkers in the pediatric population are discussed, specifically in predicting Multisystem Inflammatory Syndrome. Ultimately, biomarkers can be used as predictive tools to allow clinicians to identify and adequately manage patients at increased risk for worse outcomes from COVID-19. Both literature review and anecdotal evidence has shown that severe COVID-19 is a systemic disease, and understanding associated biomarkers are crucial for hospitalized patients' proper clinical decision-making. For example, the cytokine storm releases inflammatory markers in different organ systems such as the pulmonary, hepatobiliary, hematological, cardiac, neurological, and renal systems. This review summarizes the latest research of COVID-19 that can help inform healthcare professionals how to better mitigate morbidity and mortality associated with this disease and provides information about certain systemic biomarkers that can be incorporated into hospital practice to provide more comprehensive care for hospitalized COIVD-19 patients.
Elevated Levels of Pleiotropic Interleukin-6 (IL-6) and Interleukin-10 (IL-10) are Critically Involved With the Severity and Mortality of COVID-19: An Updated Longitudinal Meta-Analysis and Systematic Review on 147 Studies.
Jafrin S, Aziz MA, Islam MS
Biomark Insights · 2022 · PMID 35747885 · Full text
OBJECTIVES: Disruption in the natural immune reaction due to SARS-CoV-2 infection can initiate a potent cytokine storm among COVID-19 patients. An elevated level of IL-6 and IL-10 during a hyperinflammatory state plays a...
OBJECTIVES: Disruption in the natural immune reaction due to SARS-CoV-2 infection can initiate a potent cytokine storm among COVID-19 patients. An elevated level of IL-6 and IL-10 during a hyperinflammatory state plays a vital role in increasing the risk of severity and mortality. In this study, we aimed to evaluate the potential of circulating IL-6 and IL-10 levels as biomarkers for detecting the severity and mortality of COVID-19. METHODS: This study was conducted according to the Cochrane Handbook and PRISMA guidelines. Authorized databases were searched to extract suitable studies using specific search terms. RevMan 5.4 was applied for performing the meta-analysis. Mean differences in IL-6 and IL-10 levels were calculated among COVID-19 patients via a random-effects model. NOS scoring, publication bias and sensitivity analyses were checked to ensure study quality. RESULTS: A total of 147 studies were selected, with 31 909 COVID-19 patients under investigation. In the severity analysis, the mean concentration of IL-6 was significantly higher in the severe COVID-19 cases than in the non-severe cases (MD: 19.98; < .001; 95% CI: 17.56, 22.40). Similar result was observed for IL-10 mean concentration in severe COVID-19 cases (MD: 1.35; < .001; 95% CI: 0.90, 1.80). In terms of mortality analysis, circulating IL-6 showed sharp elevation in the deceased patients (MD: 42.11; < .001; 95% CI: 36.86, 47.36). IL-10 mean concentration was higher in the dead patients than in the survived patients (MD: 4.79; < .001; 95% CI: 2.83, 6.75). Publication bias was not found except for comparing IL-6 levels with disease severity. Sensitivity analysis also reported no significant deviation from the pooled outcomes. CONCLUSIONS: Elevated levels of circulating IL-6 and IL-10 signifies worsening of COVID-19. To monitor the progression of SARS-CoV-2 infection, IL-6 and IL-10 should be considered as potential biomarkers for severity and mortality detection in COVID-19. SYSTEMATIC REVIEW REGISTRATION: INPLASY registration number: INPLASY202240046.
Progress Toward a Multiomic Understanding of Traumatic Brain Injury: A Review.
Kocheril PA, Moore SC, Lenz KD … +2 more , Mukundan H, Lilley LM
Biomark Insights · 2022 · PMID 35719705 · Full text
Traumatic brain injury (TBI) is not a single disease state but describes an array of conditions associated with insult or injury to the brain. While some individuals with TBI recover within a few days or months, others p...
Traumatic brain injury (TBI) is not a single disease state but describes an array of conditions associated with insult or injury to the brain. While some individuals with TBI recover within a few days or months, others present with persistent symptoms that can cause disability, neuropsychological trauma, and even death. Understanding, diagnosing, and treating TBI is extremely complex for many reasons, including the variable biomechanics of head impact, differences in severity and location of injury, and individual patient characteristics. Because of these confounding factors, the development of reliable diagnostics and targeted treatments for brain injury remains elusive. We argue that the development of effective diagnostic and therapeutic strategies for TBI requires a deep understanding of human neurophysiology at the molecular level and that the framework of multiomics may provide some effective solutions for the diagnosis and treatment of this challenging condition. To this end, we present here a comprehensive review of TBI biomarker candidates from across the multiomic disciplines and compare them with known signatures associated with other neuropsychological conditions, including Alzheimer's disease and Parkinson's disease. We believe that this integrated view will facilitate a deeper understanding of the pathophysiology of TBI and its potential links to other neurological diseases.
Host Transcriptional Signatures Predict Etiology in Community-Acquired Pneumonia: Potential Antibiotic Stewardship Tools.
Siljan WW, Sivakumaran D, Ritz C … +6 more , Jenum S, Ottenhoff TH, Ulvestad E, Holter JC, Heggelund L, Grewal HM
Biomark Insights · 2022 · PMID 35693251 · Full text
BACKGROUND: Current approaches for pathogen identification in community-acquired pneumonia (CAP) remain suboptimal, leaving most patients without a microbiological diagnosis. If better diagnostic tools were available for...
BACKGROUND: Current approaches for pathogen identification in community-acquired pneumonia (CAP) remain suboptimal, leaving most patients without a microbiological diagnosis. If better diagnostic tools were available for differentiating between viral and bacterial CAP, unnecessary antibacterial therapy could be avoided in viral CAP patients. METHODS: In 156 adults hospitalized with CAP classified to have bacterial, viral, or mixed viral-bacterial infection based on microbiological testing or both microbiological testing and procalcitonin (PCT) levels, we aimed to identify discriminatory host transcriptional signatures in peripheral blood samples acquired at hospital admission, by applying Dual-color-Reverse-Transcriptase-Multiplex-Ligation-dependent-Probe-Amplification (dc-RT MLPA). RESULTS: In patients classified by microbiological testing, a 9-transcript signature showed high accuracy for discriminating bacterial from viral CAP (AUC 0.91, 95% CI 0.85-0.96), while a 10-transcript signature similarly discriminated mixed viral-bacterial from viral CAP (AUC 0.91, 95% CI 0.86-0.96). In patients classified by both microbiological testing and PCT levels, a 13-transcript signature showed excellent accuracy for discriminating bacterial from viral CAP (AUC 1.00, 95% CI 1.00-1.00), while a 7-transcript signature similarly discriminated mixed viral-bacterial from viral CAP (AUC 0.93, 95% CI 0.87-0.98). CONCLUSION: Our findings support host transcriptional signatures in peripheral blood samples as a potential tool for guiding clinical decision-making and antibiotic stewardship in CAP.
Volatile Organic Compounds Analysis as a Potential Novel Screening Tool for Breast Cancer: A Systematic Review.
Leemans M, Bauër P, Cuzuel V … +2 more , Audureau E, Fromantin I
Biomark Insights · 2022 · PMID 35645556 · Full text
INTRODUCTION: An early diagnosis is crucial in reducing mortality among people who have breast cancer (BC). There is a shortfall of characteristic early clinical symptoms in BC patients, highlighting the importance of in...
INTRODUCTION: An early diagnosis is crucial in reducing mortality among people who have breast cancer (BC). There is a shortfall of characteristic early clinical symptoms in BC patients, highlighting the importance of investigating new methods for its early detection. A promising novel approach is the analysis of volatile organic compounds (VOCs) produced and emitted through the metabolism of cancer cells. METHODS: The purpose of this systematic review is to outline the published research regarding BC-associated VOCs. For this, headspace analysis of VOCs was explored in patient-derived body fluids, animal model-derived fluids, and BC cell lines to identify BC-specific VOCs. A systematic search in PubMed and Web of Science databases was conducted according to the PRISMA guidelines. RESULTS: Thirty-two studies met the criteria for inclusion in this review. Results highlight that VOC analysis can be promising as a potential novel screening tool. However, results of , and case-control studies have delivered inconsistent results leading to a lack of inter-matrix consensus between different VOC sampling methods. DISCUSSION: Discrepant VOC results among BC studies have been obtained, highly due to methodological discrepancies. Therefore, methodological issues leading to disparities have been reviewed and recommendations have been made on the standardisation of VOC collection and analysis methods for BC screening, thereby improving future VOC clinical validation studies.
Identification of Potential Urinary Metabolite Biomarkers of Ventilator-Associated Pneumonia.
Jongers B, Hotterbeekx A, Bielen K … +10 more , Vervliet P, Boddaert J, Lammens C, Fransen E, Baggerman G, Covaci A, Goossens H, Malhotra-Kumar S, Jorens PG, Kumar-Singh S
Biomark Insights · 2022 · PMID 35592849 · Full text
INTRODUCTION: Ventilator-associated pneumonia (VAP) caused by is a major cause of morbidity and mortality in hospital intensive care units (ICU). Rapid identification of -derived markers in easily accessible patients' s...
INTRODUCTION: Ventilator-associated pneumonia (VAP) caused by is a major cause of morbidity and mortality in hospital intensive care units (ICU). Rapid identification of -derived markers in easily accessible patients' samples can enable an early detection of VAP (VAP-PA), thereby stewarding antibiotic use and improving clinical outcomes. METHODS: Metabolites were analysed using liquid chromatography-mass spectrometry (LC-MS) in prospectively collected urine samples from mechanically ventilated patients admitted to the Antwerp University Hospital ICU. Patients were followed from the start of mechanical ventilation (n = 100 patients) till the time of clinical diagnosis of VAP (n = 13). Patients (n = 8) in whom diagnosis of VAP was further confirmed by culturing respiratory samples and urine samples were studied for semi-quantitative metabolomics. RESULTS: We first show that multivariate analyses highly discriminated VAP-PA from VAP-non-PA as well as from the pre-infection groups ( = .97 and .98, respectively). A further univariate analysis identified 58 metabolites that were significantly elevated or uniquely present in VAP-PA compared to the VAP-non-PA and pre-infection groups ( < .05). These comprised both a known metabolite of histidine as well as a novel nicotine metabolite. Most interestingly, we identified 3 metabolites that were not only highly upregulated for, but were also highly specific to, VAP-PA, as these metabolites were completely absent in all pre-infection timepoints and in VAP-non-PA group. CONCLUSIONS: Considerable differences exist between urine metabolites in VAP-PA compared to VAP due to other bacterial aetiologies as well to non-VAP (pre-infection) timepoints. The unique urinary metabolic biomarkers we describe here, if further validated, could serve as highly specific diagnostic biomarkers of VAP-PA.
Cytokines in Abdominal Aortic Aneurysm: Master Regulators With Clinical Application.
Puchenkova OA, Soldatov VO, Belykh AE … +7 more , Bushueva O, Piavchenko GA, Venediktov AA, Shakhpazyan NK, Deykin AV, Korokin MV, Pokrovskiy MV
Biomark Insights · 2022 · PMID 35492378 · Full text
Abdominal aortic aneurysm (AAA) is a potentially life-threatening disorder with a mostly asymptomatic course where the abdominal aorta is weakened and bulged. Cytokines play especially important roles (both positive and...
Abdominal aortic aneurysm (AAA) is a potentially life-threatening disorder with a mostly asymptomatic course where the abdominal aorta is weakened and bulged. Cytokines play especially important roles (both positive and negative) among the molecular actors of AAA development. All the inflammatory cascades, extracellular matrix degradation and vascular smooth muscle cell apoptosis are driven by cytokines. Previous studies emphasize an altered expression and a changed epigenetic regulation of key cytokines in AAA tissue samples. Such cytokines as IL-6, IL-10, IL-12, IL-17, IL-33, IL-1β, TGF-β, TNF-α, IFN-γ, and CXCL10 seem to be crucial in AAA pathogenesis. Some data obtained in animal studies show a protective function of IL-10, IL-33, and canonical TGF-β signaling, as well as a dual role of IL-4, IFN-γ and CXCL10, while TNF-α, IL-1β, IL-6, IL-12/IL-23, IL-17, CCR2, CXCR2, CXCR4 and the TGF-β noncanonical pathway are believed to aggravate the disease. Altogether data highlight significance of cytokines as informative markers and predictors of AAA. Pathologic serum/plasma concentrations of IL-1β, IL-2, IL-6, TNF-α, IL-10, IL-8, IL-17, IFN-γ, and PDGF have been already found in AAA patients. Some of the changes correlate with the size of aneurysms. Moreover, the risk of AAA is associated with polymorphic variants of genes encoding cytokines and their receptors: (rs1799864), (Delta-32), (rs1800796 and rs1800795), (rs12133641), (rs1800896), (rs1800469), (rs1626340), (rs1036095, rs4522809, rs1078985), and (rs1800629). Finally, 5 single-nucleotide polymorphisms in gene coding latent TGF-β-binding protein () and an allelic variant of are related to a significantly slower AAA annual growth rate.
The Availability of Human Biospecimens to Support Biomarker Research.
Tarling TE, Byrne JA, Watson PH
Biomark Insights · 2022 · PMID 35464611 · Full text
Preserved biospecimens held in biobank inventories and clinical archives are important resources for biomarker research. Recent advances in technologies have led to an increase in use of clinical archives in particular,...
Preserved biospecimens held in biobank inventories and clinical archives are important resources for biomarker research. Recent advances in technologies have led to an increase in use of clinical archives in particular, in order to study retrospective cohorts and to generate data relevant to tissue biomarkers. This raises the question of whether the current sizes of biobank inventories are appropriate to meet the demands of biomarker research. This commentary discusses this question by considering data concerning overall biobank and biospecimen numbers to estimate current biospecimen supply and use. The data suggests that biospecimen supply exceeds current demand. Therefore, it may be important for individual biobanks to reassess the targets for their inventories, consider culling unused portions of these inventories, and shift resources towards providing prospective custom biobanking services.
Lack of Association of rs12702634 in With Interstitial Lung Diseases in Japanese Rheumatoid Arthritis Patients.
Higuchi T, Oka S, Furukawa H … +2 more , Shimada K, Tohma S
Biomark Insights · 2022 · PMID 35450030 · Full text
BACKGROUND: Rheumatoid arthritis (RA) is occasionally complicated with interstitial lung disease (ILD). A recent genome-wide association study of ILD in RA reported an association with the polymorphism rs12702634 in . We...
BACKGROUND: Rheumatoid arthritis (RA) is occasionally complicated with interstitial lung disease (ILD). A recent genome-wide association study of ILD in RA reported an association with the polymorphism rs12702634 in . We conducted an association study of this variant with ILD in Japanese RA patients to replicate this association. METHODS: Genotyping of rs12702634 was performed in 175 RA with ILD and 411 RA without chronic lung disease. RESULTS: No association was detected for rs12702634 with ILD in RA ( = .6369, odds ratio [OR] 1.13, 95% confidence interval [CI] 0.72-1.78). Meta-analysis of these data combined with the data from the recent report showed no significant association ( = .0996, OR 1.52, 95% CI 0.92-2.49). CONCLUSIONS: The present study demonstrated no association of rs12702634 with ILD in RA, suggesting the heterogeneity of the disease.
Circulating Tumor Cell-Free DNA Genes as Prognostic Gene Signature for Platinum Resistant Ovarian Cancer Diagnosis.
Gunderson CC, Radhakrishnan R, Gomathinayagam R … +5 more , Husain S, Aravindan S, Moore KM, Dhanasekaran DN, Jayaraman M
Biomark Insights · 2022 · PMID 35370397 · Full text
Clinical management of gynecological cancer begins by optimal debulking with first-line platinum-based chemotherapy. However, in ~80% patients, ovarian cancer will recur and is lethal. Prognostic gene signature panel ide...
Clinical management of gynecological cancer begins by optimal debulking with first-line platinum-based chemotherapy. However, in ~80% patients, ovarian cancer will recur and is lethal. Prognostic gene signature panel identifying platinum-resistance enables better patient stratification for precision therapy. Retrospectively collected serum from 11 "poor" (<6 months progression free interval [PFI]) and 22 "favorable" (>24 months PFI) prognosis patients, were evaluated using circulating cell-free DNA (cfDNA). DNA from both groups showed 50 to 10 000 bp fragments. Pairwise analysis of sequenced cfDNA from patients showed that gene dosages were higher for 29 genes and lower for 64 genes in poor than favorable prognosis patients. Gene ontology analysis of higher dose genes predominantly grouped into cytoskeletal proteins, while lower dose genes, as hydrolases and receptors. Higher dosage genes searched for cancer-relatedness in Reactome database indicated 15 genes were referenced with cancer. Among them 3 genes, TGFBR2, ZMIZ2, and NRG2, were interacting with more than 4 cancer-associated genes. Protein expression analysis of tumor samples indicated that TGFBR2 was downregulated and ZMIZ2 was upregulated in poor prognosis patients. Our results indicate that the cfDNA gene dosage combined with protein expression in tumor samples can serve as gene signature panel for prognosis determination amongst ovarian cancer patients.
Utilization of Prognostic Biomarker Soluble Urokinase Plasminogen Activator Receptor in the Emergency Department: A Tool for Safe and More Efficient Decision-making.
Holstein RM, Mäkinen MT, Castrén MK … +1 more , Kaartinen JM
Biomark Insights · 2022 · PMID 35295966 · Full text
INTRODUCTION: Risk stratification in the emergency departments (EDs) is in critical need for new applications due to ED overcrowding and hospitalization of older people. We aimed to evaluate the expediency, efficiency an...
INTRODUCTION: Risk stratification in the emergency departments (EDs) is in critical need for new applications due to ED overcrowding and hospitalization of older people. We aimed to evaluate the expediency, efficiency and safety of a prognostic biomarker, soluble urokinase plasminogen activator receptor (suPAR), as a tool for the risk assessment of patients arriving at the ED. METHODS: We performed a comparative cross-sectional study in 2 emergency departments (EDs), suPAR measurements being incorporated into routine blood sampling in the intervention ED. The primary outcome was the number of discharges from the ED. The importance of the outcomes was examined by appropriate multi- or bivariate analysis. RESULTS: The absolute and relative number of discharges were similar between the intervention and control groups [121 (55.3%) vs 62 (55.9%)]. No significant differences between the groups were seen in the length of stays in the ED. Patients with low suPAR values were more likely discharged and patients with high suPAR values more likely admitted to hospital. Two admitted patients with low suPAR values could have been discharged safely. CONCLUSION: The utilization of suPAR did not increase the risk for neither positive nor negative outcomes. Low suPAR values could be potential in discharging more patients safely. Instead of unselected patient populations, the benefits of suPAR measurements in the ED could emerge in the assessment of a more precisely determined and selected group of patients.
Decrease in Plasma miR-27a and miR-221 After Concussion in Australian Football Players.
Shultz SR, Taylor CJ, Aggio-Bruce R … +12 more , O'Brien WT, Sun M, Cioanca AV, Neocleous G, Symons GF, Brady RD, Hardikar AA, Joglekar MV, Costello DM, O'Brien TJ, Natoli R, McDonald SJ
Biomark Insights · 2022 · PMID 35250259 · Full text
INTRODUCTION: Sports-related concussion (SRC) is a common form of brain injury that lacks reliable methods to guide clinical decisions. MicroRNAs (miRNAs) can influence biological processes involved in SRC, and measureme...
INTRODUCTION: Sports-related concussion (SRC) is a common form of brain injury that lacks reliable methods to guide clinical decisions. MicroRNAs (miRNAs) can influence biological processes involved in SRC, and measurement of miRNAs in biological fluids may provide objective diagnostic and return to play/recovery biomarkers. Therefore, this prospective study investigated the temporal profile of circulating miRNA levels in concussed male and female athletes. METHODS: Pre-season baseline blood samples were collected from amateur Australian rules football players (82 males, 45 females). Of these, 20 males and 8 females sustained an SRC during the subsequent season and underwent blood sampling at 2-, 6- and 13-days post-injury. A miRNA discovery Open Array was conducted on plasma to assess the expression of 754 known/validated miRNAs. miRNA target identified were further investigated with quantitative real-time PCR (qRT-PCR) in a validation study. Data pertaining to SRC symptoms, demographics, sporting history, education history and concussion history were also collected. RESULTS: Discovery analysis identified 18 candidate miRNA. The consequent validation study found that plasma miR-221-3p levels were decreased at 6d and 13d, and that miR-27a-3p levels were decreased at 6d, when compared to baseline. Moreover, miR-27a and miR-221-3p levels were inversely correlated with SRC symptom severity. CONCLUSION: Circulating levels of miR-27a-3p and miR-221-3p were decreased in the sub-acute stages after SRC, and were inversely correlated with SRC symptom severity. Although further studies are required, these analyses have identified miRNA biomarker candidates of SRC severity and recovery that may one day assist in its clinical management.
Immune Checkpoint Inhibitors in Triple Negative Breast Cancer: The Search for the Optimal Biomarker.
Qureshi S, Chan N, George M … +3 more , Ganesan S, Toppmeyer D, Omene C
Biomark Insights · 2022 · PMID 35221668 · Full text
Triple negative breast cancer (TNBC) is a high-risk and aggressive malignancy characterized by the absence of estrogen receptors (ER) and progesterone receptors (PR) on the surface of malignant cells, and by the lack of...
Triple negative breast cancer (TNBC) is a high-risk and aggressive malignancy characterized by the absence of estrogen receptors (ER) and progesterone receptors (PR) on the surface of malignant cells, and by the lack of overexpression of human epidermal growth factor 2 (HER2). It has limited therapeutic options compared to other subtypes of breast cancer. There is now a growing body of evidence on the role of immunotherapy in TNBC, however much of the data from clinical trials is conflicting and thus, challenging for clinicians to integrate the data into clinical practice. Landmark phase III trials using immunotherapy in the early-stage neoadjuvant setting concluded that the addition of immunotherapy to chemotherapy improved the pathologic complete response (pCR) rate compared to chemotherapy with placebo while others found no significant improvement in pCR. Phase III trials have investigated the utility of immunotherapy in previously untreated metastatic TNBC, and these studies have similarly arrived at inconsistent conclusions. Some studies showed no benefit while others demonstrated a clinically significant improvement in overall survival in the PD-L1 positive population. It is not yet clear which biomarkers are most useful, and assays for these biomarkers have not been standardized. Given the often serious and severe side effects of immunotherapy, it is important and necessary to identify predictive biomarkers of response and resistance in order to enhance patient selection. In this review, we will discuss both the challenges of traditional biomarkers and the opportunities of emerging biomarkers for patient selection.
Mind Over Matter: Confronting Challenges in Post-Mortem Brain Biobanking for Glioblastoma Multiforme.
Griffin C, Vilain R, King S … +7 more , Nixon S, Gooley A, Bray S, Lynam J, Walker MM, Scott RJ, Paul C
Biomark Insights · 2021 · PMID 35173408 · Full text
Over the past 10 years, there has been limited progress for the treatment of brain cancer and outcomes for patients are not much improved. For brain cancer researchers, a major obstacle to biomarker driven research is li...
Over the past 10 years, there has been limited progress for the treatment of brain cancer and outcomes for patients are not much improved. For brain cancer researchers, a major obstacle to biomarker driven research is limited access to brain cancer tissue for research purposes. The Mark Hughes Foundation Brain Biobank is one of the first post-mortem adult brain banks in Australia to operate with protocols specifically developed for brain cancer. Located within the Hunter New England Local Health District and operated by Hunter Cancer Biobank, the boundaries of service provided by the Brain Bank extend well into the surrounding regional and rural areas of the Local Health District and beyond. Brain cancer biobanking is challenging. There are conflicting international guidelines for best practice and unanswered questions relating to scientific, psychosocial and operational practices. To address this challenge, a best practice model was developed, informed by a consensus of existing data but with consideration of the difficulties associated with operating in regional or resource poor settings. The regional application of this model was challenged following the presentation of a donor located in a remote area, 380km away from the biobank. This required biobank staff to overcome numerous obstacles including long distance patient transport, lack of palliative care staff, death in the home and limited rural outreach services. Through the establishment of shared goals, contingency planning and the development of an informal infrastructure, the donation was facilitated within the required timeframe. This experience demonstrates the importance of collaboration and networking to overcome resource insufficiency and geographical challenges in rural cancer research programmes.
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