-
Scientific Reports May 2022Digital counting methods were developed to decrease the high intra- and inter-observer variability of immunohistochemical markers such as Ki67, with most presenting a...
Digital counting methods were developed to decrease the high intra- and inter-observer variability of immunohistochemical markers such as Ki67, with most presenting a good correlation coefficient (CC). Since Ki67 is one of the major contributors to Oncotype DX, it is conceivable that Ki67 expression and the recurrence score (RS) obtained by the multigene panel are positively correlated. We decided first to test to what extent conventional and digital Ki67 quantification methods correlate in daily practice and, second, to determine which of these methods correlates better with the prognostic capacity of the Oncotype DX test. Both Ki67 evaluations were performed in 89 core biopsies with a diagnosis of estrogen receptor (ER) positive HER2-negative breast cancer (BC). Cases were, thus, classified twice for surrogate subtype: first by conventional analysis and then by digital evaluation. The Oncotype RS was obtained in 55 cases that were subsequently correlated to Ki67 evaluation by both methods. Conventional and digital Ki67 evaluation showed good concordance and correlation (CC = 0.81 (95% CI 0.73-0.89)). The correlation of Oncotype DX risk groups and surrogate derived subtypes was slightly higher for the digital technique (r = 0.46, p < 0.01) compared to the conventional method (r = 0.39, p < 0.01), even though both were statistically significant. In conclusion, we show that digital evaluation could be an alternative to conventional counting, and also has advantages for predicting the risk established by the Oncotype DX test in ER-positive BC. This study also supports the importance of an accurate Ki67 analysis which can influence the decision to submit ER-positive HER2-negative BC to prognostic molecular platforms.
Topics: Biomarkers, Tumor; Breast Neoplasms; Female; Humans; Ki-67 Antigen; Neoplasm Recurrence, Local; Prognosis; Receptor, ErbB-2; Receptors, Estrogen
PubMed: 35581229
DOI: 10.1038/s41598-022-11411-5 -
Clinics and Research in Hepatology and... Jun 2016Bile acid research has gained great momentum since the role of bile acids as key signaling molecules in the enterohepatic circulation was discovered. Their physiological... (Review)
Review
Bile acid research has gained great momentum since the role of bile acids as key signaling molecules in the enterohepatic circulation was discovered. Their physiological function in regulating their own homeostasis, as well as energy and lipid metabolism make them interesting targets for the pharmaceutical industry in the context of diseases such as bile acid induced diarrhea, bile acid induced cholestasis or nonalcoholic steatohepatitis. Changes in bile acid homeostasis are also linked to various types of drug-induced liver injury (DILI). However, the key question whether bile acids are surrogate markers for monitoring DILI or key pathogenic players in the onset and progression of DILI is under intense investigation. The purpose of this review is to summarize the different facets of bile acids in the context of normal physiology, hereditary defects of bile acid transport and DILI.
Topics: Bile Acids and Salts; Bile Ducts; Biological Transport; Biomarkers; Chemical and Drug Induced Liver Injury; Cholestasis, Intrahepatic; Enterohepatic Circulation; Homeostasis; Humans
PubMed: 26874804
DOI: 10.1016/j.clinre.2015.12.017 -
Oncogene Feb 2024The incidence of oropharyngeal cancer (OPSCC) has escalated in the past few decades; this has largely been triggered by high-risk human papillomavirus (HPV). Early... (Review)
Review
The incidence of oropharyngeal cancer (OPSCC) has escalated in the past few decades; this has largely been triggered by high-risk human papillomavirus (HPV). Early cancer screening is needed for timely clinical intervention and may reduce mortality and morbidity, but the lack of knowledge about premalignant lesions for OPSCC poses a significant challenge to early detection. Biomarkers that identify individuals at high risk for OPSCC may act as surrogate markers for precancer but these are limited as only a few studies decipher the multistep progression from HPV infection to OPSCC development. Here, we summarize the current literature describing the multistep progression from oral HPV infection, persistence, and tumor development in the oropharynx. We also examine key challenges that hinder the identification of premalignant lesions in the oropharynx and discuss potential biomarkers for oropharyngeal precancer. Finally, we evaluate novel strategies to improve investigations of the biological process that drives oral HPV persistence and OPSCC, highlighting new developments in the establishment of a genetic progression model for HPV + OPSCC and in vivo models that mimic HPV + OPSCC pathogenesis.
Topics: Humans; Papillomavirus Infections; Carcinoma, Squamous Cell; Papillomaviridae; Oropharyngeal Neoplasms; Biomarkers
PubMed: 38191674
DOI: 10.1038/s41388-023-02927-9 -
American Heart Journal Jun 2022The contribution of gut dysfunction to heart failure (HF) pathophysiology is not routinely assessed. We sought to investigate whether biomarkers of gut dysfunction would...
BACKGROUND
The contribution of gut dysfunction to heart failure (HF) pathophysiology is not routinely assessed. We sought to investigate whether biomarkers of gut dysfunction would be useful in assessment of HF (eg, severity, adverse outcomes) and risk stratification.
METHODS
A panel of gut-related biomarkers including metabolites of the choline/carnitine- pathway (acetyl-L-carnitine, betaine, choline, γ-butyrobetaine, L-carnitine and trimethylamine-N-oxide [TMAO]) and the gut peptide, Trefoil factor-3 (TFF-3), were investigated in 1,783 patients with worsening HF enrolled in the systems BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF) cohort and associations with HF severity and outcomes, and use in risk stratification were assessed.
RESULTS
Metabolites of the carnitine-TMAO pathway (acetyl-L-carnitine, γ-butyrobetaine, L-carnitine, and TMAO) and TFF-3 were associated with the composite outcome of HF hospitalization or all-cause mortality at 3 years (hazards ratio [HR] 2.04-2.93 [95% confidence interval {CI} 1.30-4.71] P≤ .002). Combining the carnitine-TMAO metabolites with TFF-3, as a gut dysfunction panel, showed a graded association; a greater number of elevated markers was associated with higher New York Heart Association class (P< .001), higher plasma concentrations of B-type natriuretic peptide (P< .001), and worse outcome (HR 1.90-4.58 [95% CI 1.19-6.74] P≤ 0.008). Addition of gut dysfunction biomarkers to the contemporary BIOSTAT HF risk model also improved prediction for the aforementioned composite outcome (C-statistics P≤ .011, NRI 13.5-21.1 [95% CI 2.7-31.9] P≤ .014).
CONCLUSIONS
A panel of biomarkers of gut dysfunction showed graded association with severity of HF and adverse outcomes. Biomarkers as surrogate markers are potentially useful for assessment of gut dysfunction to HF pathophysiology and in risk stratification.
Topics: Acetylcarnitine; Biomarkers; Carnitine; Choline; Chronic Disease; Heart Failure; Humans
PubMed: 35278373
DOI: 10.1016/j.ahj.2022.03.002 -
Current Heart Failure Reports Aug 2022Survival outcomes for heart transplant recipients have improved in recent decades, but infection remains a significant cause of morbidity and mortality. In this review,... (Review)
Review
PURPOSE OF REVIEW
Survival outcomes for heart transplant recipients have improved in recent decades, but infection remains a significant cause of morbidity and mortality. In this review, we discuss several biological markers, or biomarkers, that may be used to monitor immunologic status in this patient population.
RECENT FINDINGS
While modest, data on the utility of immune biomarkers in heart transplant recipients suggest correlation between low level of immune response and increased infection risk. More novel assays, such as the detection of circulating levels of pathogen cell-free DNA in plasma and the use of Torque teno virus load as a surrogate for net state of immunosuppression, have potential to be additional important biomarkers. Biomarker approaches to individualize immunosuppression therapy among heart transplant recipients is a promising area of medicine. However, additional studies are needed to inform the optimal protocol in which to incorporate these biomarkers into clinical practice.
Topics: Biomarkers; Heart Failure; Heart Transplantation; Humans; Torque teno virus; Viral Load
PubMed: 35597863
DOI: 10.1007/s11897-022-00556-z -
Psychoneuroendocrinology Jul 2024Recent research shows prominent effects of pregnancy and the parenthood transition on structural brain characteristics in humans. Here, we present a comprehensive study...
Recent research shows prominent effects of pregnancy and the parenthood transition on structural brain characteristics in humans. Here, we present a comprehensive study of how parental status and number of children born/fathered links to markers of brain and cellular ageing in 36,323 UK Biobank participants (age range 44.57-82.06 years; 52% female). To assess global effects of parenting on the brain, we trained a 3D convolutional neural network on T1-weighted magnetic resonance images, and estimated brain age in a held-out test set. To investigate regional specificity, we extracted cortical and subcortical volumes using FreeSurfer, and ran hierarchical clustering to group regional volumes based on covariance. Leukocyte telomere length (LTL) derived from DNA was used as a marker of cellular ageing. We employed linear regression models to assess relationships between number of children, brain age, regional brain volumes, and LTL, and included interaction terms to probe sex differences in associations. Lastly, we used the brain measures and LTL as features in binary classification models, to determine if markers of brain and cellular ageing could predict parental status. The results showed associations between a greater number of children born/fathered and younger brain age in both females and males, with stronger effects observed in females. Volume-based analyses showed maternal effects in striatal and limbic regions, which were not evident in fathers. We found no evidence for associations between number of children and LTL. Classification of parental status showed an Area under the ROC Curve (AUC) of 0.57 for the brain age model, while the models using regional brain volumes and LTL as predictors showed AUCs of 0.52. Our findings align with previous population-based studies of middle- and older-aged parents, revealing subtle but significant associations between parental experience and neuroimaging-based surrogate markers of brain health. The findings further corroborate results from longitudinal cohort studies following parents across pregnancy and postpartum, potentially indicating that the parenthood transition is associated with long-term influences on brain health.
Topics: Humans; Female; Male; Brain; Adult; Middle Aged; Aged; Magnetic Resonance Imaging; Aged, 80 and over; Cellular Senescence; Parents; Neural Networks, Computer; Aging; Telomere; Biomarkers; Leukocytes; Parenting
PubMed: 38636355
DOI: 10.1016/j.psyneuen.2024.107040 -
Journal of Neurochemistry Jan 2022Regenerating Family Member 3 Alpha (REG3A) is a multifunctional protein with antimicrobial activity, and primarily secreted by the intestine and pancreas. Studies have...
Regenerating Family Member 3 Alpha (REG3A) is a multifunctional protein with antimicrobial activity, and primarily secreted by the intestine and pancreas. Studies have shown an increased expression of REG3A in systemic inflammatory responses to acute injury and infection, but studies investigating REG3A during the pathogenesis of ischemic stroke are limited. The aims of this study were to examine the associations between arterial expression of REG3A and other arterial inflammatory proteins implicated in stroke pathogenesis, as well as associations between REG3A and markers of poor outcome for ischemic stroke. The University of Kentucky Blood and Clot Thrombectomy Registry and Collaboration (BACTRAC) protocol (clinicaltrials.gov NCT03153683) utilizes thrombectomy to isolate intracranial arterial blood (i.e. distal to thrombus) and systemic arterial blood (i.e. carotid). Samples were analyzed by Olink Proteomics for N = 42 subjects. Statistical analyses of plasma proteins included 2-sample t-tests, spearman and biserial correlations, and robust regression models to elucidate network signaling and association to clinical outcomes. Results indicated that levels of systemic REG3A were positively correlated with inflammatory proteins interleukin IL6 (R = 0.344, p = 0.030) and IL17C (R = 0.468, p = 0.002). 2-sided t- tests examining differences of systemic REG3A within quartiles of NIHSS admission score depicted significant differences between quartiles. Those with NIHSS scores corresponding to moderate and moderate-severe neurofunctional deficits had significantly higher levels of systemic REG3A compared to those with NIHSS scores corresponding to mild and mild-moderate neurofunctional deficits (p = 0.016). STRING analyses of proteins in each robust regression model demonstrated substantial networking between REG3A and other systemic proteins highly relevant to ischemic stroke. The present study provides novel data on systemic REG3A in the context of ischemic stroke. These results demonstrate the influential role of REG3A regarding surrogate functional and radiographic outcomes of stroke severity. Additionally, they provide novel insight into the role of REG3A and related proteins during the complex neuroinflammatory process of ischemic stroke. These data provide a foundation for future studies to investigate REG3A and related networking proteins as potential biomarkers with prognostic potential, as well as potential therapeutic targets.
Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Female; Humans; Ischemic Stroke; Male; Middle Aged; Pancreatitis-Associated Proteins; Prognosis; Signal Transduction
PubMed: 34558059
DOI: 10.1111/jnc.15520 -
Glia Oct 2016There is a growing understanding that aberrant GLIA function is an underlying factor in psychiatric and neurological disorders. As drug discovery efforts begin to focus... (Review)
Review
There is a growing understanding that aberrant GLIA function is an underlying factor in psychiatric and neurological disorders. As drug discovery efforts begin to focus on glia-related targets, a key gap in knowledge includes the availability of validated biomarkers to help determine which patients suffer from dysfunction of glial cells or who may best respond by targeting glia-related drug mechanisms. Biomarkers are biological variables with a significant relationship to parameters of disease states and can be used as surrogate markers of disease pathology, progression, and/or responses to drug treatment. For example, imaging studies of the CNS enable localization and characterization of anatomical lesions without the need to isolate tissue for biopsy. Many biomarkers of disease pathology in the CNS involve assays of glial cell function and/or response to injury. Each major glia subtype (oligodendroglia, astroglia and microglia) are connected to a number of important and useful biomarkers. Here, we describe current and emerging glial based biomarker approaches for acute CNS injury and the major categories of chronic nervous system dysfunction including neurodegenerative, neuropsychiatric, neoplastic, and autoimmune disorders of the CNS. These descriptions are highlighted in the context of how biomarkers are employed to better understand the role of glia in human CNS disease and in the development of novel therapeutic treatments. GLIA 2016;64:1755-1771.
Topics: Biomarkers; Central Nervous System Diseases; Humans; Neuroglia
PubMed: 27228454
DOI: 10.1002/glia.22998 -
Annals of Medicine Dec 2022Previous study have shown that lipid accumulation product (LAP), visceral adiposity index (VAI), triglyceride/high-density lipoprotein cholesterol ratio (TG/HDL-C) and...
OBJECTIVE
Previous study have shown that lipid accumulation product (LAP), visceral adiposity index (VAI), triglyceride/high-density lipoprotein cholesterol ratio (TG/HDL-C) and triglycerides/glucose index (TyG index) could be simple clinical indicators of insulin resistance (IR) based on anthropometric and/or biochemical parameters. However, the rational and preferred surrogate marker of IR in different population has yet to be validated. The aim of this study was evaluating the practicability of the LAP, VAI, TG/HDL-C, and TyG in predicting IR in middle-aged Chinese population.
METHODS
A cross-sectional study was conducted in 569 Chinese participants (mean age was 48.5; man 67.7%), and each participant completed a questionnaire survey, anthropometric measurement, and biochemical testing. One-way ANOVAs, Chi-squared test, Pearson's correlation, and multiple logistic regression were used to evaluate the association between VAI, LAP, TG/HDL-C, and TyG with IR. To correctly discriminate individuals with insulin resistance, a receiver operating characteristic (ROC) analysis was conducted for each evaluated variable and the overall diagnostic accuracy was quantified using the area under the ROC curve (AUC). The AUC of evaluated variables were compared using a nonparametric approach. The optimal cut-off points were determined by the Youden's index, and the corresponding sensitivity and specificity were provided.
RESULTS
Significant positive correlation was identified between HOMA-IR with TG/HDL-C ( = 0.306), VAI ( = 0.217), LAP ( = 0.381), and TyG ( = 0.371), respectively (all < .001). After adjustment for potential confounders of IR, compared with the lowest tertiles, odds ratio (95% CI) having IR in the highest tertiles of TG/HDL-C, VAI, LAP and TyG were 6.07 (2.89-12.71), 10.89 (4.37-27.13), 4.68 (2.00-10.92), and 12.20 (5.04-29.56). The area under ROC curves to predict HOMA-diagnosed IR was 0.773 for TG/HDL-C, 0.767 for VAI, 0.806 for LAP, and 0.800 for TyG, respectively. Among those, LAP showed the greatest value of AUC [0.806 (0.763-0.850)] and highest specificity (0.804).
CONCLUSION
Compared with other indicators, the LAP and TyG are simple, relatively accurate, clinically available surrogate markers of insulin resistance in middle-aged population in Hefei, China. Among 4 evaluated parameters, the LAP have the highest specificity and the TyG have the highest sensitivity.Key MessagesLAP and TyG could be used as simple and alternative methods to identify the individuals at risk for insulin resistance.LAP and TyG have relatively high predictive ability in diagnosis of IR compared with VAI and TG/HDL-C.No significant difference is observed between LAP and TyG in the ability of predicting insulin resistance.
Topics: Biomarkers; Blood Glucose; China; Cholesterol, HDL; Cross-Sectional Studies; Humans; Insulin Resistance; Lipid Accumulation Product; Male; Middle Aged; Triglycerides
PubMed: 35175162
DOI: 10.1080/07853890.2022.2039956 -
Journal of Diabetes Investigation Mar 2018The present study evaluated the ability of lipid accumulation product (LAP), visceral adiposity index (VAI), and the product of triglycerides and glucose (TyG), three...
AIMS/INTRODUCTION
The present study evaluated the ability of lipid accumulation product (LAP), visceral adiposity index (VAI), and the product of triglycerides and glucose (TyG), three novel markers, in identifying metabolic syndrome (MetS) with different criteria in middle-aged and elderly Chinese.
MATERIALS AND METHODS
During June 2012 to January 2013, 992 consecutive patients (age ≥40 years) were enrolled at Daping Hospital. The criteria of MetS were based on the International Diabetes Federation and the modified National Cholesterol Education Program's Adult Treatment Panel III. VAI, LAP and TyG were computed based on a published mathematical model.
RESULTS
The prevalence of MetS was 42.8%. The receiver operating characteristic curve found LAP, VAI and TyG were positively related to MetS in both criteria. The optimal cut-offs of VAI, LAP and TyG for the modified National Cholesterol Education Program's Adult Treatment Panel III and International Diabetes Federation criteria were 2.015, 31.465 and 8.706, and 2.035, 37.99 and 8.697, respectively. After adjustment of potential confounding factors, VAI, LAP and TyG were significantly correlated with MetS in all criteria according to optimal cut-offs. For MetS, reliable predictive value was observed in different subgroups (age and sex). LAP showed the greatest area under the curve in MetS with the International Diabetes Federation definition (area under the curve 0.887, 95% confidence interval 0.852-0.922).
CONCLUSIONS
AP, VAI and TyG were reliable surrogate markers for identifying MetS in middle-aged and elderly Chinese. LAP could be a better parameter than VAI and TyG for predicting MetS in the present study.
Topics: Aged; Asian People; Biomarkers; Blood Glucose; China; Female; Humans; Intra-Abdominal Fat; Lipid Accumulation Product; Male; Metabolic Syndrome; Middle Aged; Sensitivity and Specificity; Triglycerides
PubMed: 28664593
DOI: 10.1111/jdi.12708