Biomarkers For Early Detection Research Articles

Metabolomic Insights into Smoking-Induced Metabolic Dysfunctions: A Comprehensive Analysis of Lipid and Amino Acid Metabolomes

Background: Cigarette smoking is a leading cause of preventable mortality, largely due to the absence of effective, non-invasive biomarkers for early disease detection. Profiling serum metabolomics to identify metabolic changes holds the potential to accelerate the detection process and identify individuals at risk of developing smoking-related diseases. Objectives: This study investigated the biochemical and metabolomic changes induced by nicotine exposure, with a focus on disruptions in amino acid, lipid, and carbohydrate metabolism. Methods: Liquid chromatography–tandem mass spectrometry (LC-MS/MS) was employed to observe significant disruptions in lipid and amino acid metabolism, along with alterations in key metabolic pathways. A total of 400 smokers and 100 non-smokers were included to evaluate the biomarkers related to insulin resistance, blood lipid profile, inflammation, and kidney and liver function. Results: The results demonstrated significantly elevated (p < 0.05) levels of glycemic markers in smokers, including fasting blood glucose; glycated hemoglobin (HbA1c); and inflammatory markers such as interleukin-6 (IL-6) and C-reactive protein (CRP). Smokers also exhibited dyslipidemia, with increased total cholesterol (154.888 ± 35.565) and LDL levels (117.545 ± 24.138). Impaired liver and kidney function was evident, with significantly higher levels (p < 0.05) of AST, ALP, ALT, blood urea nitrogen, and creatinine in smokers. A total of 930 metabolites were identified, of which 343 exhibited significant alterations (p < 0.05) in smokers compared to non-smokers. Among these, 116 metabolites were upregulated, and 127 were downregulated. Metabolomic pathway analysis revealed eight significant pathways. The study also identified three lipid metabolites specific to smokers and seven unique to non-smokers. Through LC-MS/MS, fragments of phenylalanine, tryptophan, valine, histidine, carnitine, and sphinganine were detected. Several lipidomic changes associated with insulin resistance and cardiovascular complications were observed. Cadmium (Cd) levels were higher in smokers than non-smokers (1.264 ppb vs. 0.624 ppb) and showed a strong negative correlation (R2 = 0.8061, p-value = 0.015) with serum zinc (Zn), likely due to Cd displacing Zn in proteins and causing nephrotoxicity through accumulation. Conclusions: This study highlights the distinct metabolic disruptions caused by smoking that could serve as potential biomarkers for the early detection of metabolic diseases. It emphasizes the importance of metabolomics in identifying systemic indicators of smoking-related health issues, providing new opportunities for preventive and therapeutic interventions.

Nailfold capillary abnormalities as indicators of diabetic nephropathy progression: a cross-sectional study in type 2 diabetes

Background Type 2 diabetes mellitus (DM) leads to chronic hyperglycemia and microvascular complications, including diabetic nephropathy (DN). Nailfold videocapillaroscopy (NVC) is a non-invasive method for assessing the microvascular abnormalities and may aid in early DN detection. This study investigates the correlation between DN and nailfold capillary abnormalities in type 2 DM. Methods This prospective cross-sectional study involved 453 participants with type 2 DM, divided into 3 groups based on estimated glomerular filtration rate (eGFR) or albumin-to-creatinine (A/C) ratio. Chronic kidney disease (CKD) risk categories based on the 2012 Kidney Disease Improving Global Outcomes (KDIGO) guidelines. Participants underwent structured interviews, clinical assessments, and laboratory tests. NVC was performed to assess capillary morphology, distribution, density, and blood flow. Results Significant differences in NVC measurements were observed across eGFR groups, with higher NVC scores and more severe capillary abnormalities noted in lower eGFR groups. The ‘comma-like’ capillary distribution pattern (23.08%, p = 0.016), more ratio of ramified capillaries (p = 0.0137) were observed in the eGFR <30 ml/min/1.73m2 group. Reduced fundus transparency (p = 0.0015) and impaired visibility of the sub-venous plexus (p = 0.0016) were noted in the lower eGFR groups. Capillary lengths, both input and mean, were shorter in the A/C ratio > 300 mg/g group (p = 0.0382 and p = 0.0478, respectively). The NVC score was higher in the A/C ratio > 300 mg/g groups (p = 0.0028). Conclusion Nailfold capillary abnormalities correlate with DN severity, indicating their potential as a non-invasive biomarker for early DN detection and monitoring in type 2 DM.

Harnessing Epigenetics: Innovative Approaches in Diagnosing and Combating Viral Acute Respiratory Infections

Abstract: Acute respiratory infections (ARIs) caused by viruses such as SARS-CoV-2, influenza viruses, and respiratory syncytial virus (RSV), pose significant global health challenges, particularly for the elderly and immunocompromised individuals. Substantial evidence indicates that acute viral infections can manipulate the host’s epigenome through mechanisms like DNA methylation and histone modifications as part of the immune response. These epigenetic alterations can persist beyond the acute phase, influencing long-term immunity and susceptibility to subsequent infections. Post-infection modulation of the host epigenome may help distinguish infected from uninfected individuals and predict disease severity. Understanding these interactions is crucial for developing effective treatments and preventive strategies for viral ARIs. This review highlights the critical role of epigenetic modifications following viral ARIs in regulating the host’s innate immune defense mechanisms. We discuss the implications of these modifications for diagnosing, preventing, and treating viral infections, contributing to the advancement of precision medicine. Recent studies have identified specific epigenetic changes, such as hypermethylation of interferon-stimulated genes in severe COVID-19 cases, which could serve as biomarkers for early detection and disease progression. Additionally, epigenetic therapies, including inhibitors of DNA methyltransferases and histone deacetylases, show promise in modulating the immune response and improving patient outcomes. Overall, this review provides valuable insights into the epigenetic landscape of viral ARIs, extending beyond traditional genetic perspectives. These insights are essential for advancing diagnostic techniques and developing innovative treatments to address the growing threat of emerging viruses causing ARIs globally.

Abstract WP227: Physiological Magnetic Resonance Imaging Biomarkers for Early Detection of Microvascular Dysfunction in Acute Intracerebral Hemorrhage

Abstract WP227: Physiological Magnetic Resonance Imaging Biomarkers for Early Detection of Microvascular Dysfunction in Acute Intracerebral Hemorrhage

The utility of neurofilament light chain in conjunction with clinical biomarkers for early detection and prediction of disease burden and severity in neuronopathic Gaucher disease

The utility of neurofilament light chain in conjunction with clinical biomarkers for early detection and prediction of disease burden and severity in neuronopathic Gaucher disease

Effects of endocrine disrupting chemicals, blood metabolome, and epigenetics on breast cancer risk: A multi-dimensional mendelian randomization study.

Current research on the relationship between environmental endocrine disrupting chemicals (EDCs) and breast cancer remains insufficient, with limited evidence and inconsistent conclusions. Mendelian randomization (MR) is a robust method for establishing causality, as it reduces biases from confounding factors and reverse causation. This study uses MR to investigate the effects of three types of EDCs, including bisphenols, parabens, and phthalates, on the risk of overall breast cancer and its subtypes-Luminal A, Luminal B, triple negative, human epidermal growth factor receptor 2-enriched, and estrogen receptor-positive/negative. The study also examines the 1400 blood metabolome as potential mediators and explores EDCs-associated DNA methylation changes as potential factors, with a focus on European populations. Our results shows that n-butyl paraben (n-BuP) is positively associated with Luminal A, mono-methyl phthalate is negatively associated with Luminal B, and mono-iso-butyl phthalate (MiBP) is positively associated with triple negative breast cancer (TNBC). Mediation analysis reveals that blood metabolites, such as caffeic acid sulfate and the caffeine-to-paraxanthine ratio, mediate the effect of n-BuP on Luminal A, while methylsuccinate mediate the effect of MiBP on TNBC. Epigenetic analysis shows associations between EDCs exposure-related DNA methylation changes at specific CpG sites (cg26325335, cg08537847, cg27454300) and different breast cancer risks. These findings not only suggest potential biomarkers for early detection and intervention but also underscore the imperative for further research to rigorously validate these associations.

Exosomal insights into ovarian cancer stem cells: revealing the molecular hubs

Ovarian cancer is a deadly disease, often diagnosed at advanced stages due to a lack of reliable biomarkers. Exosomes, which carry a variety of molecules such as proteins, lipids, DNA, and non-coding RNAs, have recently emerged as promising tools for early cancer detection. While exosomes have been studied in various cancer types, comprehensive network analyses of exosome proteins in ovarian cancer remain limited. In this study, we used a protein-protein interaction (PPI) network. Using the Clustermaker2 app and the MCODE algorithm, we identified six significant clusters within the network, highlighting regions involved in functional pathways. A four-fold algorithmic approach, including MCC, DMNC, Degree, and EPC, identified 12 common hub genes. STRING analysis and visualization techniques provided a detailed understanding of the biological processes associated with these hub genes. Notably, 91.7% of the identified hub genes were involved in translational processes, showing an important role in protein synthesis regulation in ovarian cancer. In addition, we identified the miRNAs and LncRNAs carried by ovarian cancer exosomes. These findings highlight potential biomarkers for early detection and therapeutic targets.

LINE-1 Retrotransposons as Cell-free DNA Biomarkers for Multi-Cancer Early Detection.

LINE-1 retrotransposons, comprising 17% of the genome, drive cancer instability through hypomethylation. The DIAMOND assay, targeting LINE-1 hypomethylation with bisulfite sequencing of cell free DNA, achieved AUCs of 88% to 100% across six cancer types, surpassing mutation-based diagnostics and suggesting utility in early cancer detection and management.

COMPARATIVE ANALYSIS OF THE TOTAL PROTEOME IN NONALCOHOLIC STEATOHEPATITIS: IDENTIFICATION OF POTENTIAL BIOMARKERS.

Nonalcoholic fatty liver disease (NAFLD) is a hepatic condition characterized excessive fat accumulation in the liver with advanced stage nonalcoholic steatohepatitis (NASH), potentially leading to liver fibrosis, cirrhosis, and cancer. Currently, the identification and classification of NASH require invasive liver biopsy, which has certain limitations. Mass spectrometry-based proteomics can detect crucial proteins and pathways implicated in NASH development and progression. We collected liver and serum samples from choline-deficient, L-amino acid-defined high-fat diet fed NASH C57BL/6J mice and human serum samples to examine proteomic alterations and identify early biomarkers for NASH diagnosis. In-depth targeted multiple reaction monitoring (MRM) scanning and immunoblotting assays were used to verify the biomarker candidates from mouse liver and serum samples, and enzyme-linked immunosorbent assay (ELISA) was employed to analyze human serum samples. The MRM analysis of NASH liver revealed 50 proteins with altered expression (18 up- and 32 downregulated) that are involved in biological processes such as detoxification, fibrosis, inflammation, and fatty acid metabolism. Ingenuity pathway analysis identified impaired protein synthesis, cellular stress and defense, cellular processes and communication, and metabolism in NASH mouse liver. Immunoblotting analysis confirmed that the expression of proteins associated with fatty acid metabolism (Aldo B and Fasn) and urea cycle (Arg1, Cps1, and Otc) was altered in mouse liver and serum. Further analysis on human serum samples using ELISA confirmed the increased expression of multiple proteins, including Aldo B, Asl, and Lgals3, demonstrating values of 0.917, 0.979, and 0.965 of area under the curve in NASH diagnosis. These findings offer valuable insights into the molecular mechanisms of NASH and possible diagnostic biomarkers for early detection.

Urinary Chemistry in Healthy Cross-bred Pet Rabbits (Oryctolagus cuniculus) and Rabbits with Suspected Chronic Kidney Disease

Abstract Renal biomarkers for early detection of decreased kidney function have been extensively studied in dogs and cats, but there is limited research for pet rabbits. Specifically, studies on urinary indices for cross-bred rabbits are scarce. Therefore, this study aimed to assess the potential use of urinalysis in cross-bred pet rabbits. Urine samples from 30 healthy crossbred pet rabbits and 11 rabbits with suspected kidney disease (KD) from three clinics were collected. Reference intervals of urinary indices, including urinary protein, creatinine (uCRE), urinary protein-to-creatinine (UPC) ratio, gamma-glutamyl transferase (uGGT), and uGGT ratio, were established and compared to two published reference intervals (RIs). The results showed that healthy rabbits consistently had low urine protein levels and abnormal UPC ratios, compared to a published study involving only pure-bred rabbits. Rabbits with KD had higher urine protein levels and significantly higher UPC ratio (p&amp;lt;0.001), with 63% having ratios greater than 0.4. Additionally, rabbits with KD showed significantly (p&amp;lt;0.001) lower uCRE levels and urine specific gravity (USG) with elevated uGGT index (p&amp;lt;0.05), compared to the healthy group. Significant differences (p&amp;lt;0.05) were also observed in urine color, turbidity, pH, and positivity of the occult blood by dipstick. This study underscores potential breed-specific variations in urinary protein levels and UPC ratio, as well as highlights the diagnostic potential of USG, UPC ratio, and uGGT index in rabbits with KD. However, the presence of breed-specific variations and technical nuances in laboratory equipment necessitate careful interpretation of results. Therefore, further studies across larger and more diverse rabbit populations are crucial to validate the diagnostic performance of urinary indices in diagnosing KD in rabbits.

PTM-Fetuin-A: A Novel Biomarker for Early Detection of Diabetic Kidney Disease

PTM-Fetuin-A: A Novel Biomarker for Early Detection of Diabetic Kidney Disease

Enhanced ZBTB10 expression induced by betulinic acid inhibits gastric cancer progression by inactivating the ARRDC3/ITGB4/PI3K/AKT pathway.

Gastric cancer (GC) ranks as the fourth leading cause of cancer-related deaths worldwide, with most patients diagnosed at advanced stages due to the absence of reliable early detection biomarkers. RNA-sequencing was conducted to identify the differentially expressed genes between GC tissues and adjacent normal tissues. CCK8, EdU, colony formation, transwell, flow cytometry and xenograft assays were adopted to explore the biological function of ZBTB10 and betulinic acid (BA) in GC progression. RNA-sequencing and phospho-proteomic profiling were performed to analyze the signaling pathways associated with ZBTB10-inhibiting GC progression. Chromatin immunoprecipitation, Co-immunoprecipitation and luciferase reporter assay were employed to elucidate the potential molecular regulatory mechanisms of ZBTB10 in GC. ZBTB10 was one of the most significantly downregulated genes in GC tissues, and higher expression levels of ZBTB10 was correlated with better prognosis in patients with GC. Functional studies revealed that ZBTB10 overexpression and BA inhibited GC progression both in vitro and in vivo. Mechanistically, ZBTB10 enhanced ARRDC3 expression by binding to a specific response element in the ARRDC3 promoter region. Elevated ARRDC3 then directly interacted with β-4 integrin (ITGB4), leading to its ubiquitination and degradation. This cascade ultimately resulted in the downregulation of PI3K and AKT phosphorylation level. Moreover, ZBTB10 was a key target for BA in GC and BA inhibited GC progression through regulating the ZBTB10/ARRDC3/ITGB4/PI3K/AKT axis. Our findings reveal that BA holds promise as an effective therapeutic strategy for GC, and the ZBTB10/ARRDC3/ITGB4/PI3K/AKT axis may serve as a novel diagnostic and therapeutic target.

The emerging role of blood-based biomarkers in early detection of colorectal cancer: A systematic review.

Colorectal cancer (CRC), the third most commonly diagnosed and second most lethal cancer worldwide, necessitates efficient early detection strategies to improve patient outcomes. This review evaluates the promise of novel blood-based biomarkers for early detection of CRC. A systematic review, registered with PROSPERO (CRD42024513770) and adhering to PRISMA guidelines, was conducted across multiple databases from January 1st, 2020 to December 31st, 2022. The comprehensive search strategy centered on sensitivity, specificity, and AUC-ROC of multiple types of molecular blood biomarkers. Of total of 142 included articles, 59 were on protein, 58 on RNA, and 21 on DNA. The investigation into DNA biomarkers revealed that cfDNA and ctDNA carry significant potential for early CRC diagnosis. For instance, methylation patterns in genes such as MYO1-G and NDRG4 exhibited high diagnostic accuracies with AUCs reaching up to 0.996. RNA biomarkers like miRNAs and circRNAs also showed promising results, with circ_0011536 achieving AUCs of 0.982. Protein biomarkers, contrasted with established cancer markers, unveiled notable candidates like Irisin and ANXA2, with AUCs surpassing 0.96. The review highlights several individual markers and panels with the potential to improve upon existing CRC screening tests. Despite the promise shown by the novel biomarkers, challenges persist, including small sample sizes, potential selection biases, and a lack of comprehensive cost-effectiveness analysis. Future research should focus on large-scale, multicenter, prospective studies across diverse populations. The findings advocate for an integrated biomarker approach, potentially revolutionizing CRC screening and aligning it with clinical realities through rigorous validation.

Non-invasive diagnosis for urothelial carcinoma using a dual-target DNA methylation biomarker panel.

Urothelial carcinoma (UC) is a common malignancy worldwide. Aberrant DNA methylation is implicated in UC carcinogenesis. This study sought to delineate the DNA methylation landscape in UC and identify DNA methylation-based biomarkers for early detection of UC. Whole genome bisulfite sequencing (WGBS) was conducted on bladder cancer tissues and paired normal tissues. By integrating WGBS data with The Cancer Genome Atlas (TCGA) UBC data, a DNA methylation-based biomarker was identified. When combined with a known UC biomarker AL021918.2, the performance of the dual-target test was evaluated in voided urine samples from 224 UC patients and 419 controls. Notable hypomethylation was observed in UC samples compared to normal samples. Through differential methylation analysis, differential methylation CpG sites, regions, and genes were identified. Of these, Transmembrane protein 106A gene (TMEM106A) was screened as a new UC biomarker. In a dual-target test, using triplex quantitative methylation-specific PCR (qMSP) to examine TMEM106A and AL021918.2 methylation levels, the training set showed a sensitivity of 89.0%, a specificity of 92.9%, and an area under the curve (AUC) value of 0.941 (95% confidence interval [CI]: 0.913-0.969). Similarly, the validation set showed a sensitivity of 90.0%, a specificity of 91.1%, and an AUC value of 0.922 (95% CI: 0.881-0.962). Thus, our dual-target test demonstrated outstanding detection rates for low-grade or early-stage tumors. We provide a comprehensive analysis of DNA methylation profiles in UC, and highlight the promising clinical potential of dual-target urine tests for UC detection.

Non-linear relationship between urinary creatinine and diabetic kidney disease: implications for clinical practice

ObjectiveThis study aims to investigate the relationship between urinary creatinine (UCr) and the risk and severity of Diabetic Kidney Disease (DKD) in patients with Type 2 Diabetes Mellitus (T2DM). The goal is to establish UCr as a potential biomarker for early DKD detection and severity assessment.MethodsA retrospective cross-sectional analysis was conducted using medical records of T2DM patients. Patients were classified into groups with and without DKD, and relevant clinical data, including demographic, blood, and urine parameters, were collected. Logistic regression and receiver operating characteristic (ROC) curve analysis evaluated the association between UCr levels and DKD. Curve fitting and threshold effect model were used to further evaluate the relationship between UCr and the incidence and severity of DKD.ResultsA total of 302 T2DM patients were analyzed, with 137 diagnosed with DKD. Significant differences in clinical parameters were observed between the DKD and non-DKD groups, particularly in UCr, urine albumin levels, and eGFR. UCr levels demonstrated a strong association with DKD. Moreover, a non-linear relationship was identified, with specific inflection points indicating different correlation patterns of UCr with DKD occurrence and progression.ConclusionThe findings of this study highlight the potential of UCr as a valuable biomarker for early detection and assessment of DKD in T2DM patients. Incorporating UCr measurements into routine clinical practice could enhance early identification of patients at risk for kidney complications, leading to timely intervention and improved patient outcomes.

PTM-Fetuin-A: A Novel Biomarker for Early Detection of Diabetic Kidney Disease

Chronic Kidney Disease (CKD) is a significant public health issue with a rising prevalence globally. Diabetic kidney disease (DKD), a leading cause of CKD, necessitates improved biomarkers for early detection and effective management. Traditional markers such as serum creatinine, estimated glomerular filtration rate (eGFR), and albuminuria have notable limitations in sensitivity and specificity, especially for early detection. Fetuin-A, specifically its post-translationally modified form (PTM-Fetuin-A), has emerged as a potential novel biomarker for DKD. This study evaluates PTM-Fetuin-A in a cohort of Bulgarian patients with type 1 and type 2 diabetes, assessing its correlation with traditional markers such as albuminuria and eGFR. Significant correlations were observed between PTM-Fetuin-A and these indicators (e.g., Pearson’s r = 0.447, p = 0.025 for albuminuria), highlighting its ability to detect early kidney function decline. Furthermore, PTM-Fetuin-A demonstrated potential as a non-invasive tool for identifying normoalbuminuric DKD, addressing gaps left by conventional biomarkers. By offering additional prognostic value, PTM-Fetuin-A could improve the early diagnosis and clinical management of diabetic patients, reducing the burden of CKD.

Could serum Raftlin and GPER-1levels be new biomarkers for early detection of non-small cell lung cancer?

BackgroundLung cancer is the leading cause of cancer-related deaths worldwide. Therefore, the search for new biomarkers continues in order to diagnose lung cancer at an early stage. In this study, we investigated blood levels of G-protein associated membrane estrogen receptor (GPER)-1 and Raftlin as markers of early-stage in lung cancer.MethodsLung cancer cases admitted to our hospital between 2016 and 2018 were included in our study. GPER-1 and Raftlin levels were measured by Enzyme-Linked Immunosorbent Assay (ELISA) in blood samples taken from patients diagnosed with lung cancer and healthy volunteers.ResultsThere were 64 cases in total, 32 cases in lung cancer group and 32 cases in control group. We evluated GPER-1 levels for each group. GPER-1 level was 2.54 (IQR: 1.08–5.78) ng/mL in the lung cancer group and 5 (IQR: 2.69–7.99) ng/mL in the control group. ROC analysis value for GPER-1, (AUC) was 0.66 (p < 0.01). Raftlin levels were 4.5 (IQR: 3.3-11.52) ng/mL in control group and 7.77 (IQR: 6.24–9.85) ng/mL in lung cancer group. ROC analysis value for Raftlin, (AUC) was 0.629(P = 0.09).ConclusionsIn our study, there was no statistically significant difference between our groups in terms of Raftlin values. Therefore, it was thought that Raftlin could not be a specific marker in the diagnosis of lung cancer. GPER-1 was found to be lower in the lung cancer group than in healthy individuals. Therefore, it was thought that GPER-1 could be evaluated as a diagnostic marker in lung cancer. However, we think that more definitive results can be obtained by determining the tissue and expression level of GPER in lung cancer with further studies.

Development a glycosylated extracellular vesicle-derived miRNA Signature for early detection of esophageal squamous cell carcinoma

BackgroundEsophageal squamous cell carcinoma (ESCC) is often diagnosed at an advanced stage due to the lack of non-invasive early detection tools, which significantly impacts patient prognosis. Given that glycosylation alterations especially high sialylation and fucosylation, frequently occur during cellular malignant transformation, but their roles are not elucidated. We examined alterations in disease-specific glycosylated extracellular vesicles (EVs)-derived miRNAs in the serum of ESCC patients, evaluating their utility as diagnostic biomarkers.MethodsA total of 371 ESCC and 303 healthy controls (HCs) were recruited in this multi-stage, multicentre case-control study. Fucosylated (Fuc-) and sialylated (Sia-) EVs were isolated utilizing Lentil lectin (LCA) and wheat germ lectin (WGA)-coated magnetic beads, respectively. The glycosylated EVs-derived miRNAs-based signature (RiskscoreFuc−&Sia−) was established through logistic regression in a training cohort and subsequently validated in an internal and an external multicentre cohort.ResultsThe RiskscoreFuc−&Sia− effectively identified ESCC across all stages, demonstrating high AUC values in training (0.980), internal validation (0.957), and external multicentre validation (0.973) cohorts, markedly higher than carcinoembryonic antigen (CEA) (AUC = 0.769, training cohort; AUC = 0.749, internal validation cohort; AUC = 0.765, external validation cohort). Notably, this score exhibited robust accuracy in detecting CEA (-) ESCC cases (CEA < 5 ng/ml) (AUC = 0.974, training & internal cohort; AUC = 0.973, external multicentre validation cohort). Additionally, it displayed strong efficacy in differentiating early-stage ESCC patients (AUC = 0.982, training cohort; AUC = 0.977, external multicentre validation cohort).ConclusionsOur study illustrates the effectiveness of glycosylated EVs capture strategy for isolating tumour-specific EVs. The unique glycosylated EVs-derived miRNAs-based signature shows the optimal potential as a biomarker for early detection of ESCC.Graphical

CA-125 as a Biomarker in Renal Medullary Carcinoma: Integrated Molecular Profiling, Functional Characterization, and Prospective Clinical Validation.

Renal medullary carcinoma (RMC) is a highly aggressive malignancy defined by the loss of the SMARCB1 tumor suppressor. It mainly affects young individuals of African descent with sickle cell trait, and it is resistant to conventional therapies used for other renal cell carcinomas. This study aimed to identify potential biomarkers for early detection and disease monitoring of RMC. Integrated profiling of primary untreated RMC tumor tissues and paired adjacent kidney controls was performed using RNA-sequencing (RNA-seq) and histone Chromatin Immunoprecipitation Sequencing (ChIP-seq). The expression of serum cancer antigen 125 (CA-125), was prospectively evaluated in 47 patients with RMC. Functional studies were conducted in RMC cell lines to assess the effects of SMARCB1 re-expression. MUC16, encoding for CA-125, was identified as one of the top upregulated genes in RMC tissues, with concomitant enrichment of active histone marks H3K4me3 and H3K27ac at its promoter. Elevated serum CA-125 levels were found in 31 of 47 (66%) RMC patients and correlated significantly with metastatic tumor burden (p = 0.03). Functional studies in RMC cell lines demonstrated that SMARCB1 re-expression significantly reduced MUC16 expression. The correlation between serum CA-125 levels and metastatic burden suggests that CA-125 is a clinically relevant biomarker for RMC. These findings support further exploration of CA-125 for disease monitoring and targeted therapeutics in RMC.

Plasma Endothelin-1 Levels: Non-Predictors of Alzheimer's Disease Reveal Age Correlation in African American Women.

Background/Objectives: Alzheimer's disease (AD) and related dementias (ADRD) disproportionately impact racial and ethnic minorities. Contributing biological factors that explain this disparity have been elusive. Moreover, non-invasive biomarkers for early detection of AD are needed. Endothelin-1 (ET-1), a vasoconstrictive factor linked to cerebral vascular disease pathology and neuronal injury, could provide insights to better understand racial disparities in AD. As a potent vasoconstrictive peptide that regulates contractions in smooth muscle, endothelial cells, and pericytes, ET-1 may result in cerebral vascular constriction, leading to cerebral hypoperfusion; over time, this may result in neuronal injury, contributing to the pathology of AD. The role of the ET-1 system as a driver of ethnic disparities in AD requires further investigation. In the United States (U.S.), ET-1 dysregulation in Hispanic/Latinx (H/L) ethnic populations has largely been unexplored. Genetics linking ET-1 dysregulation and racial disparities in AD also require further investigation. In this study, we examined the role of the ET-1 protein in human plasma as a potential biomarker with predictive value for correlating with the development of AD by age, race, and sex. Methods: We examined ET-1 protein levels using quantitative mass spectrometry in AA and NHW patients with AD, along with controls. Results: A partial correlation between age at draw and ET-1, stratified by race and sex, while controlling for AD status, was significant for female AAs (r = 0.385, p = 0.016). When the data were not stratified but controlled for AD status, the partial correlation between age at draw and ET-1 was not significant (r = 0.108, p = 0.259). Conclusions: Based on the small number of plasma specimens and no plasma specimens from H/L individuals with AD, we conclude that ET-1 was clearly not a significant factor in predicting AD in this study and will require a larger scale study for validation.