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PubMed2004

Genomic biomarkers for cancer assessment: implementation challenges for laboratory practice.

Genomic biomarkers are an emerging class of laboratory tests, which present special implementation challenges for clinical laboratory services, compared to conventional laboratory tests. These challenges, which include analytical, bioinformatics, bioethical, interpretation and commercialization issues, represent real obstacles to widespread implementation of these tests. Technical challenges include the capacity to detect and identify many different kinds of markers for different diseases in a short time period, capacity to identify simultaneously gene rearrangements, amplification, inhibition, deletions and replications. Bioinformatics challenges include rapid analysis of genomic data, as well as the cross reference to other genomic data, and to other laboratory tests. Bioethical issues relate to consent to retain and use genetic data, which may be obtained inadvertently during analysis for genomic markers. Interpretation challenges include observations that the particular genomic markers may not be independent variables, as other undetected genomic alterations could invalidate or alter genomic marker interpretation. Further, as early experience with predictive genetic markers for cancer has shown, proprietary commercial interests may conflict with public health values of identifying genomic markers in subject populations. Based on our 10 years of experience with genomic biomarkers, important implementation strategies for genomic markers include development of:Standard high throughput analyzers capable of detecting any alteration of any genomic variant at any time. Bioinformatics analysis online, coupled to stored patient data. Laboratory service framework that preserves confidentiality but integrates genomic data with other laboratory tests. Laboratory service framework, which links consents, genomic analysis, reports to both specimen and data repositories. Overall, the laboratory service challenges for genomic markers are to manage very large analytical sets and very large data sets in finite time with responsible interpretation, all within finite funding. To meet these challenges, implementation strategies beyond the one disease, one diagnosis, one genomic marker concept must begin now.

Biomarkers, Tumor↗

PubMed2025

Baseline metabolomic profile as potential biomarker for weight change after Roux-en-Y gastric bypass (RYGB) surgery.

Metabolic and bariatric surgery (MBS) is the most effective intervention for sustained weight loss and cardiometabolic improvement in individuals with severe obesity. However, long-term outcomes vary, with many patients experiencing weight regain. The biological determinants of this variability remain incompletely understood. Given the integrative nature of the metabolome-capturing interactions among host genetics, diet, microbiota, and environmental exposures-we hypothesized that baseline circulating metabolites could stratify individuals into distinct long-term weight trajectory groups. We profiled untargeted fasting plasma metabolites in a nested case-control study within the Longitudinal Assessment of Bariatric Surgery (LABS-2) cohort. From these metabolites, a 13-metabolite risk score (MetRS) predictive of weight regain five years after Roux-en-Y gastric bypass was derived. The MetRS, which captures pathways including fatty acid oxidation, bile acid conjugation, and microbial-host co-metabolism, outperformed clinical variables in predicting long-term weight outcomes. Its performance was evaluated in two independent cohorts, including one assessed a median of seven years post-surgery. Genomic analyses identified common variants in loci including AGXT2 and SLC7A5 associated with key MetRS metabolites, suggesting a heritable component to the observed metabolic signature. Together, these findings lay the groundwork for a clinically actionable framework to identify individuals at risk for weight recidivism and support the integration of metabolic profiling into preoperative assessment for personalized obesity care.

Journal Article↗

PubMed2006

Platelet C4d is highly specific for systemic lupus erythematosus.

OBJECTIVE: Complement-activation product C4d is deposited on normal erythrocytes, while abnormal levels have been observed on the surface of erythrocytes of patients with systemic lupus erythematosus (SLE). This study examines whether C4d also deposits on human platelet surfaces, and whether platelet-bound C4d may provide a biomarker for SLE. METHODS: We conducted a cross-sectional study of 105 patients with SLE, 115 patients with other diseases, and 100 healthy controls. Levels of C4d on the surface of platelets were examined by flow cytometry and scanning confocal microscopy. Statistical analyses were performed to determine the clinical variables associated with platelet C4d. RESULTS: Abnormal levels of platelet C4d were found to be highly specific for SLE. Platelet C4d was detected in 18% of patients with SLE, being 100% specific for a diagnosis of SLE compared with healthy controls and 98% specific for SLE compared with patients with other diseases (P < 0.0001). In addition, platelet C4d was significantly associated with positivity for lupus anticoagulant (P < 0.0001) and anticardiolipin antibodies of the IgG (P = 0.035) or the IgM (P = 0.016) isotype. Platelet C4d was also significantly associated with SLE disease activity according to the SLE Disease Activity Index (P = 0.039), low serum C4 (P = 0.046), an elevated erythrocyte sedimentation rate (P = 0.006), and abnormal levels of C4d on erythrocytes (P < 0.0001). CONCLUSION: This observation suggests that platelet-bound C4d may be a useful biomarker for SLE and may be a clue to the pathogenic mechanisms responsible for the myriad thrombotic and vascular complications of lupus associated with antiphospholipid antibodies.

Adult↗

PubMed2003

Evaluating prey capture by larval mummichogs (Fundulus heteroclitus) as a potential biomarker for contaminants.

We evaluated larval prey capture as a "behavioral biomarker" of contamination by examining feeding behavior of larval mummichogs (Fundulus heteroclitus) from many different sites, including a severely contaminated "Superfund" site, moderately contaminated sites, and reference areas. Prey capture ability was related to sediment contaminant levels. The levels of contaminants at a site were highly correlated with each other, so that the impact of individual contaminants was confounded. The number of captures of brine shrimp by mummichog larvae from all sites was highly variable, but significant negative correlations of prey capture were seen with mercury, lead, zinc, cadmium, and PCBs. As observed previously with adults, polyaromatic hydrocarbons (PAHs) did not appear to impair prey capture ability. The only site in which prey capture rates of 8-day old larvae were severely affected was the most highly contaminated Superfund site, Berry's Creek, NJ. This implies that larval prey capture is not as sensitive a behavioral biomarker for contamination as adult behavior studied previously.

Animals↗

PubMed2026

Non-small cell lung cancer and tumor-educated platelets: screening of biomarkers and construction of a prognostic model.

BACKGROUND: Lung cancer is a leading cause of cancer-related mortality worldwide, emphasizing the urgent need for effective early detection strategies. Traditional Chinese medicine (TCM) provides a unique perspective on tumor pathogenesis, focusing on concepts such as "long-term stasis leading to accumulation". Tumor-educated platelets (TEPs) offer potential as biomarkers due to their ability to reflect cancer heterogeneity and facilitate less invasive diagnostic approaches. This study aims to identify TEP-related prognostic biomarkers for non-small cell lung cancer (NSCLC) and to construct and validate a multigene prognostic model by integrating platelet transcriptomic data with tumor tissue datasets. METHODS: We performed comprehensive analysis of gene expression datasets obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) repositories to characterize transcriptomic differences among lung cancer specimens, normal tissue samples, and TEPs. Using R software, we identified Differentially expressed genes (DEGs) and subsequently applied a multi-stage analytical pipeline to TEP-associated DEGs, incorporating univariate Cox proportional hazards regression, least absolute shrinkage and selection operator (LASSO) regression, multivariate Cox regression, and stepwise regression modeling to pinpoint genes with prognostic significance. These prognostically relevant genes served as the foundation for developing a risk stratification model. We computed individual risk scores across both training and validation cohorts, enabling patient stratification into high- and low-risk categories. Model robustness was assessed through internal cross-validation and external validation procedures, while predictive performance was quantified using risk calibration metrics and receiver operating characteristic (ROC) curve analysis. RESULTS: Through systematic bioinformatics screening, we identified a four-gene prognostic signature comprising NELL2, C4orf48, PRAM1, and KLHL35, which served as the foundation for developing our risk stratification algorithm. Rigorous internal cross-validation and external cohort validation substantiated the moderate predictive performance of this signature. Comprehensive clinicopathological correlation analysis revealed that elevated risk indices, advanced pathological staging (stage III-IV), increased primary tumor dimensions, regional lymph node metastasis, and distant organ dissemination each demonstrated statistically significant associations with diminished overall survival (OS) outcomes in lung cancer patients. The clinical nomogram exhibited acceptable calibration, with calibration plots showing reasonable concordance between predicted and observed survival probabilities across all time points. Discriminative capacity assessment via time-dependent ROC analysis yielded area under the curve (AUC) values consistently surpassing 0.6, confirming moderate prognostic discrimination. Furthermore, decision curve analysis (DCA) demonstrated that our integrated multi-gene model conferred potential net clinical benefit compared to individual prognostic variables across the full spectrum of clinically relevant threshold probabilities (0-1 range), thereby establishing its potential utility for risk-informed clinical decision-making. CONCLUSIONS: This study identified NELL2, C4orf48, PRAM1, and KLHL35 as candidate TEP-related prognostic biomarkers for non-small cell lung cancer (NSCLC). The developed prognostic model shows preliminary potential for patient stratification, but its clinical application, particularly as a platelet-based liquid biopsy tool, requires further validation in independent TEP-based cohorts.

Tumor-educated platelets (TEPs)↗

PubMed2002

Weight-loss attempts and reporting of foods and nutrients, and biomarkers in a national cohort.

OBJECTIVE: This study examined the reported intake of foods and nutrients, and biomarkers of dietary exposure and cardiovascular disease in relation to history of trying to lose weight. METHODS: Dietary, anthropometric and biochemical data were from the third National Health and Nutrition Examination Survey (1988-1994), n=13 092. The history of attempting weight loss variable was created as follows: trying to lose currently and tried in the past 12 months (Y/Y); trying to lose currently, but not tried in the past 12 months (Y/N), not trying currently, but tried in the past 12 months (N/Y); not trying now and not tried in the past 12 months (N/N). Multiple regression methods were used to examine the independent association of history of trying to lose weight with reported intakes of energy, nutrients, percentage energy from low-nutrient-dense foods (sweeteners, baked and dairy desserts, visible fats and salty snacks), and serum concentrations of vitamins, carotenoids and lipids. RESULTS: Men and women in the Y/Y group reported lower energy intake relative to the N/N group (P<0.0000). However, the reported percentage energy from fat and carbohydrate by the Y/Y group did not differ from the N/N group. Percentage of energy from low-nutrient-dense foods was lower in men in the Y/Y group but not women. The relative odds of reporting the estimated average requirement (EAR) of folate, and vitamins A, B(6), B(12), C, E and iron and adequate intake (AI) of calcium were not adversely affected by history of trying to lose weight in men. In women, the odds of meeting the folate and vitamin E EAR were lower in the Y/Y group. Some history of weight loss categories were significant positive predictors of serum vitamin and carotenoid concentrations, or unrelated to cardiovascular disease risk biomarkers. CONCLUSIONS: There was little evidence for increased nutritional risk in those reporting repeat attempts at weight loss.

Adult↗

PubMed2005

A Bayesian approach to jointly modeling toxicity and biomarker expression in a phase I/II dose-finding trial.

In this article, we propose a Bayesian approach to phase I/II dose-finding oncology trials by jointly modeling a binary toxicity outcome and a continuous biomarker expression outcome. We apply our method to a clinical trial of a new gene therapy for bladder cancer patients. In this trial, the biomarker expression indicates biological activity of the new therapy. For ethical reasons, the trial is conducted sequentially, with the dose for each successive patient chosen using both toxicity and activity data from patients previously treated in the trial. The modeling framework that we use naturally incorporates correlation between the binary toxicity and continuous activity outcome via a latent Gaussian variable. The dose-escalation/de-escalation decision rules are based on the posterior distributions of both toxicity and activity. A flexible state-space model is used to relate the activity outcome and dose. Extensive simulation studies show that the design reliably chooses the preferred dose using both toxicity and expression outcomes under various clinical scenarios.

Algorithms↗

PubMed2026

CircExor enables interpretable prediction of circRNA localization into extracellular vesicles.

Certain circular RNAs (circRNAs) are selectively enriched in extracellular vesicles (EVs), in which they contribute to intercellular communication and represent promising biomarkers, yet the sequence determinants of their sorting remain unclear. Existing computational predictors are optimized mainly for linear RNAs and rarely address circRNA localization into EVs. Here we introduce circExor, the first framework specifically designed for circRNA EV localization. We curate a dedicated benchmark data set of 2102 circRNAs and implement a variable-length end-to-end concatenation strategy together with k-mer frequency encoding to accommodate circular topology, long sequence length, and length heterogeneity. Using a tree-based classifier, circExor achieves superior performance compared with RNAlocate-v3 and ExoGRU, reaching an AUROC of 0.743 on the internal test set and an average AUROC of 0.680 on the held-out test set. SHAP-based analysis, sequence perturbation analysis, motif mapping, and cell-based experimental validation support the predicted EV tendency and identify YBX1, HNRNPK, HNRNPL, and NOVA2 as candidate RBPs potentially associated with circRNA sorting. CircExor therefore provides a predictive and interpretable framework that links in silico modeling to mechanistic hypotheses, and supports biomarker discovery and candidate prioritization for downstream studies of EV-associated circRNAs.

Journal Article↗

PubMed2006

Small protein biomarkers of culture in Bacillus spores detected using capillary liquid chromatography coupled with matrix assisted laser desorption/ionization mass spectrometry.

Capillary liquid chromatography (cLC) coupled with matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOF-MS) was used to compare small proteins and peptides extracted from Bacillus subtilis spores grown on four different media. A single, efficient protein separation, compatible with MALDI-MS analysis, was employed to reduce competitive ionization between proteins, and thus interrogate more proteins than possible using direct MALDI-MS. The MALDI-MS data files for each fraction are assembled as two-dimensional data sets of retention time and mass information. This method of visualizing small protein data required careful attention to background correction as well as mass and retention time variability. The resulting data sets were used to create comparative displays of differences in protein profiles between different spore preparations. Protein differences were found between two different solid media in both phase bright and phase dark spore phenotype. The protein differences between two different liquid media were also examined. As an extension of this method, we have demonstrated that candidate protein biomarkers can be trypsin digested to provide identifying peptide fragment information following the cLC-MALDI experiment. We have demonstrated this method on two markers and utilized acid breakdown information to identify one additional marker for this organism. The resulting method can be used to identify discriminating proteins as potential biomarkers of growth media, which might ultimately be used for source attribution.

Amino Acid Sequence↗

PubMed2005

Internet-based Profiler system as integrative framework to support translational research.

BACKGROUND: Translational research requires taking basic science observations and developing them into clinically useful tests and therapeutics. We have developed a process to develop molecular biomarkers for diagnosis and prognosis by integrating tissue microarray (TMA) technology and an internet-database tool, Profiler. TMA technology allows investigators to study hundreds of patient samples on a single glass slide resulting in the conservation of tissue and the reduction in inter-experimental variability. The Profiler system allows investigator to reliably track, store, and evaluate TMA experiments. Here within we describe the process that has evolved through an empirical basis over the past 5 years at two academic institutions. RESULTS: The generic design of this system makes it compatible with multiple organ system (e.g., prostate, breast, lung, renal, and hematopoietic system,). Studies and folders are restricted to authorized users as required. Over the past 5 years, investigators at 2 academic institutions have scanned 656 TMA experiments and collected 63,311 digital images of these tissue samples. 68 pathologists from 12 major user groups have accessed the system. Two groups directly link clinical data from over 500 patients for immediate access and the remaining groups choose to maintain clinical and pathology data on separate systems. Profiler currently has 170 K data points such as staining intensity, tumor grade, and nuclear size. Due to the relational database structure, analysis can be easily performed on single or multiple TMA experimental results. The TMA module of Profiler can maintain images acquired from multiple systems. CONCLUSION: We have developed a robust process to develop molecular biomarkers using TMA technology and an internet-based database system to track all steps of this process. This system is extendable to other types of molecular data as separate modules and is freely available to academic institutions for licensing.

Automation↗

PubMed1998

The characterization of micro-organisms by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

A variety of gram-positive and gram-negative intact bacterial cells have been analysed by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) and shown to provide fingerprint mass spectra with discrete peaks being observed over the mass range from 3 to 40 kDa. The spectra show both more peaks and peaks at a higher mass/charge ratio than have hitherto been reported for these micro-organisms and would appear to provide a profile of cellular proteinaceous material. The spectra are shown to be reproducible over variable time periods of up to three months and factors affecting reproducibility are discussed. The procedure, which requires minimal sample preparation, yields results in 30-40 minutes and allows visual identification of species- and strain-specific biomarkers for the characterization of the organisms. The importance of accurately defining sample preparation methodologies is central to the ability of the technique to generate reliable and reproducible data.

Bacterial Proteins↗

PubMed2002

Population dynamics of type I and II methanotrophic bacteria in rice soils.

Methane-oxidizing bacteria (methanotrophs) consume a significant but variable fraction of greenhouse-active methane gas produced in wetlands and rice paddies before it can be emitted to the atmosphere. Temporal and spatial dynamics of methanotroph populations in California rice paddies were quantified using phospholipid biomarker analyses in order to evaluate the relative importance of type I and type II methanotrophs with depth and in relation to rice roots. Methanotroph population fluctuations occurred primarily within the top 0-2 cm of soil, where methanotroph cells increased by a factor of 3-5 over the flooded rice-growing season. The results indicate that rice roots and rhizospheres were less important than the soil-water interface in supporting methanotroph growth. Both type I and type II methanotrophs were abundant throughout the year. However, only type II populations were strongly correlated with soil porewater methane concentrations and rice growth.

Carbon Radioisotopes↗

PubMed1989

Epidemiology and risk factors.

HBC is common, accounting for approximately 9% of the total breast cancer burden. Given 142,000 cases of breast cancer expected to occur in 1989, this would represent 12,780 cases of HBC patients. Soberingly, each patient represents a family with a variable number of inordinately high risk patients. HBC's natural history is distinctive and enables the identification of at risk patients who can benefit from highly targeted surveillance/management strategies. High priority must be given to development of biomarkers that will one day be found to have acceptable sensitivity and specificity to genotype status. Thus, we would then be able to tell which of the first-degree relatives of affected members have inherited the deleterious gene. This would result in a significant saving of time and money that would otherwise be expended through intensive surveillance strategies. We need cost-benefit research to induce third party carriers to defray expenses for surveillance. Finally, priority attention must be given to biomolecular research for identification of markers of acceptable sensitivity and specificity to the cancer-prone genotype. Eventual cloning of the deleterious gene(s) could lead to knowledge about its chemical and physiologic products, thereby enabling anticancer pharmacologic research. The reward could then be improved control and even prevention of breast cancer, and possibly of the associated cancers in heterogenous forms of this disease.

Adult↗

PubMed2005

Precocious puberty in adolescent girls: a biomarker of later psychosocial adjustment problems.

We have investigated the hypothesis that stress condition will accelerate pubertal maturation in adolescent girls and that faster maturing girls will display more behavioral problems than their on-time or late-maturing peers during pubertal development. Longitudinal data were collected yearly from 1986 to 1997. Parents of 1039 French-speaking Canadian girls completed a questionnaire about their characteristics as well as those of their family. To predict onset of puberty by time and cumulative risk factors, a Hierarchical Regression Analysis and a Survival Regression Analysis were conducted. Results revealed that: (1) anxiety at 8 years old, lower level of anxiety a year earlier and more adverse family condition predict a younger age at first menses; and (2) Body Mass Index, conflicts, and sleep disturbances significantly predict the onset of puberty. Complementary standard regression analyses demonstrated that situational stress mediated the effect of these variables. We concluded that precocious puberty could be an indicator of stress in a child, thus, allowing professionals to intervene early and to prevent later problems in psychosocial adjustment.

Adjustment Disorders↗

PubMed1993

Surrogate endpoints in chemoprevention of breast cancer: guidelines for evaluation of new biomarkers.

Markers of early events in the development of breast cancer are potential candidates for surrogate endpoints in chemoprevention trials. There are many such markers and the challenge is to identify truly relevant markers. If successful, surrogate endpoints offer several potential benefits in the conduct of prevention trials, including: shorter latency and hence shorter trials; reductions in size and cost of trials; and the opportunity to study prevention measures where use of primary outcomes would be excessively invasive or unethical. Although there are currently no validated surrogate endpoints for breast cancer, criteria for the discovery and validation of surrogates have been proposed. Putative surrogate endpoints should be biologically plausible, represent an early event in the causal pathway, be measurable by a standardized and reliable assay, and exhibit a dose-response. Perhaps most importantly, surrogates should statistically capture the effect of the intervention on outcome. The identification and establishment of a biomarker as a valid surrogate for cancer is a stepwise process that involves both smaller "transitional" studies and larger second-generation chemoprevention trials in which both primary outcome and putative surrogates are measured. Transitional studies are used to move new markers from the laboratory into use in human populations, and are designed to address specific questions of assay validity, treatment/marker associations, marker/disease associations, and inter- and intra-individual variability. Promising markers should be added to current and planned, large, traditionally designed chemoprevention trials in order to definitively address the issues of optimal representation, and to test the adequacy with which the marker(s) captures the effect of treatment on outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers, Tumor↗

PubMed1991

Human monoclonal antibodies against blood group antigens preferentially express a VH4-21 variable region gene-associated epitope.

An anti-idiotypic antibody has been raised which recognizes human immunoglobulins with cold agglutinin activity of anti-I/i specificity. The pattern of reactivity of the antibody indicates that the structural basis for the epitope is located in the VH4-21 gene segment of the VHIV family, which is preferentially utilized by these cold reactive antibodies. Using this antibody, epitope expression was investigated in a panel of 72 human monoclonal allo-antibodies specific for human blood group antigens, as compared with a control panel of 39 randomly selected human monoclonal IgM antibodies of unknown specificities. The anti-blood group panel included 44 IgM and 28 IgG monoclonal antibodies against a variety of blood group antigens including the A antigen, Rh C, c, D, E, e, G antigens, and the Kidd antigens Jka and Jkb. The epitope was expressed by 64% (28/44) of the IgM anti-blood group antibodies and by 21% (6/28) of the IgG antibodies, but by only 7.7% (3/39) of the control IgM antibodies. These data indicate that the human alloimmune response to blood group antigens is biased in the use of VH gene families, with a preference for the VH4-21 gene segment of the VHIV family, or closely related gene segments. The fact that this mirrors the findings for the autoimmune cold agglutinins suggests a link in immunoglobulin gene usage between antibodies against structurally diverse antigens on the red cell surface.

Antibodies, Monoclonal↗

PubMed2006

The associations between socioeconomic status, allostatic load and measures of health in older Taiwanese persons: Taiwan social environment and biomarkers of aging study.

Data from a national representative sample of 1023 elderly and near-elderly Taiwanese were used to explore whether allostatic load is associated with health outcomes and mediates the association between socioeconomic status and health in a non-Western population. The information collected included: demographic characteristics; allostatic load scores; socioeconomic status, measured by education and income; health behaviours; health-related variables, including self-rated health, basic activities of daily living difficulties, instrumental activities of daily living difficulties, and physical activity difficulties. The adjusted prevalent odds ratios of higher allostatic load level were 1.25 (95% CI: 1.00, 1.56) for reporting one level worse in self-rated health and 1.43 (95% CI: 1.14, 1.82) for reporting one more physical activity difficulty. There were significant associations of lower education or less income with worse self-rated health and more difficulties with physical functioning. The associations between education, income and health status are not mediated by the conventional ten-point measure of allostatic load in older Taiwanese adults.

Age Factors↗

PubMed2003

Identification of serum soluble ST2 receptor as a novel heart failure biomarker.

BACKGROUND: Using genomic technology, we previously identified an interleukin-1 receptor family member, ST2, as a gene markedly induced by mechanical strain in cardiac myocytes. The soluble receptor form of ST2 is secreted and detectable in human serum. This study tested the hypothesis that soluble ST2 levels in the serum of patients with severe chronic heart failure are increased in patients with neurohormonal activation. METHODS AND RESULTS: Serum samples, clinical variables, and neurohormone levels from the PRAISE-2 heart failure trial (NYHA functional class III-IV; end point, mortality or transplantation) were analyzed. ST2 serum measurements were performed with ELISA on samples from 161 patients obtained at trial enrollment and from 139 of the same patients obtained 2 weeks after trial enrollment. Baseline ST2 levels were correlated with baseline B-type natriuretic peptide (BNP) levels (r=0.36, P<0.0001), baseline proatrial natriuretic peptide (ProANP) levels (r=0.36, P<0.0001), and baseline norepinephrine levels (r=0.39, P<0.0001). The change in ST2 was significant as a univariate predictor of subsequent mortality or transplantation (P=0.048), as was baseline BNP (P<0.0001) and baseline ProANP (P<0.0001). In multivariate models including BNP and ProANP, the change in ST2 remained significant as a predictor of mortality or transplantation independent of BNP and ProANP. CONCLUSIONS: Serum soluble ST2 is a novel biomarker for neurohormonal activation in patients with heart failure. In patients with severe chronic NYHA class III to IV heart failure, the change in ST2 levels is an independent predictor of subsequent mortality or transplantation.

Adolescent↗