Biomarker Insights[JOURNAL]
Sun
200 papers
Extracellular Matrix-Related Prognostic Signature for Head and Neck Squamous Cell Carcinoma via Multi-Algorithm Survival Modeling.
Chen W, Liu Y
Biomark Insights · 2026 · PMID 42367224 · Full text
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) has a poor prognosis, and the extracellular matrix (ECM) plays a key role in tumor progression, emerging as a potential biomarker for prognosis and therapy. OBJEC...
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) has a poor prognosis, and the extracellular matrix (ECM) plays a key role in tumor progression, emerging as a potential biomarker for prognosis and therapy. OBJECTIVES: To develop and validate an ECM-related prognostic signature (ECMS) and assess its association with immune features and therapeutic response in HNSCC. DESIGN: Retrospective, multi-cohort bioinformatics and experimental study integrating transcriptomic analysis, machine learning, and molecular biology validation. METHODS: ECM-related genes were identified from transcriptome data. An ECMS was constructed using 10 machine learning algorithms with 101 algorithm combinations and evaluated across training, internal, and external validation cohorts. An integrated nomogram combining ECMS with clinical variables was developed for prognosis prediction. Immune infiltration and treatment responses were analyzed. qRT-PCR validated gene expression in 15 paired HNSCC and adjacent normal tissues, and molecular experiments confirmed key gene functions. RESULTS: Twenty-three ECM genes were significantly associated with prognosis. The ECMS demonstrated moderate and consistent predictive performance across datasets. The nomogram provided a potential tool for clinical outcome prediction. Significant differences in immune cell infiltration and immune checkpoint gene expression were observed between high- and low-risk groups. qRT-PCR confirmed elevated expression of key ECM genes, including WNT7A, in tumor tissues, and functional assays showed that WNT7A promotes HNSCC cell proliferation, migration, and invasion. CONCLUSION: This study developed an ECMS with potential prognostic value, which may complement existing clinical variables for outcome prediction in HNSCC.
Salivary Biomarkers for Diagnosis and Monitoring of Thyroid Diseases: A Systematic Review of Current Evidence.
Krithika C, Sridhar C, Santhanakrishnan S … +3 more , Mahendra J, Sankari L, Sivakumar T
Biomark Insights · 2026 · PMID 42318276 · Full text
BACKGROUND: Thyroid hormones have a crucial impact on all physiological systems. Diagnosis of thyroid diseases using salivary biomarkers is an emerging discipline and requires consolidation of existing information. AIMS:...
BACKGROUND: Thyroid hormones have a crucial impact on all physiological systems. Diagnosis of thyroid diseases using salivary biomarkers is an emerging discipline and requires consolidation of existing information. AIMS: This systematic review is aimed at identifying and analyzing salivary biomarkers that are associated with thyroid diseases and evaluate their potential as diagnostic applicability as non-invasive indicators of thyroid dysfunction. METHODOLOGY: Literature search was conducted in PubMed, Cochrane, EBSCO, ProQuest, and Google Scholar from date of inception to May 2025. Human observational studies, clinical trials, and diagnostic accuracy studies published in the English language, that related biomarkers in saliva to thyroid diseases were collected and analyzed for relevant information. The search resulted in 35 records, followed by PRISMA 2020 compliant screening which resulted in 9 records included for data synthesis. Data extraction, tabulation and Risk of Bias assessment was carried out by 2 independent reviewers. RESULTS: Included studies suggest that FT3, amino acids, salivary metabolic profiling, glycan profiles, microbiome, and thyroid antibodies present in saliva could be putative and noninvasive biomarkers of diagnostic and prognostic importance. CONCLUSION: Heterogeneity in study design and analytical techniques has limited definitive conclusions about said markers, necessitating future well-designed clinical studies for validation of these biomarkers for noninvasive thyroid screeing and diagnosis.
Urinary Calprotectin Predicts Severe Acute Kidney Injury After Non-cardiac Surgery in Surgical Intensive Care Unit: A Prospective Cohort Study.
Yao W, Xu L, Li N … +6 more , Wang J, Zhou Q, Tang L, Zheng X, Li S, Yang L
Biomark Insights · 2026 · PMID 42256875 · Full text
BACKGROUND: Postoperative risk stratification for severe acute kidney injury (AKI) can facilitate timely intervention and improve prognosis. OBJECTIVES: This study aimed to evaluate the added predictive ability of urinar...
BACKGROUND: Postoperative risk stratification for severe acute kidney injury (AKI) can facilitate timely intervention and improve prognosis. OBJECTIVES: This study aimed to evaluate the added predictive ability of urinary calprotectin for postoperative risk stratification of severe AKI in non-cardiac surgery patients. DESIGN: A total of 580 patients were enrolled, and 98 (17%) developed severe AKI with a median time of 12.8 hours after SICU admission. METHODS: In a prospective cohort of patients transferred to the surgical intensive care unit (SICU) after non-cardiac surgery, calprotectin was measured in urine samples collected 0, 6, and 12 hours after SICU admission. A clinical model for predicting severe AKI was established. We tested the ability of urinary calprotectin alone to predict severe AKI by area under the receiver operating characteristics curve (AUC) analysis. We further evaluated the improvement of the pre-diction ability after adding urinary calprotectin in the clinical model by the increment in AUC, relevant integrated discrimination improvement (IDI), and net reclassification improvement (NRI). RESULTS: Higher urinary calprotectin levels were observed in the severe AKI group at any time point (All P<0.001). In the entire cohort, the AUC of urinary calprotectin at SICU admission for predicting severe AKI was 0.701(95% CI, 0.649 to 0.754), and calprotectin ≥32.3 ng/ml was associated with increased risk (OR 6.119, 95% CI 3.259 - 11.488). The AUC of the clinical model increased from 0.693 (95%CI, 0.633 to 0.754) to 0.730 (95%CI, 0.677 to 0.784) upon adding urinary calprotectin, the NRI was 0.337 (P<0.001) and the IDI was 0.055 (P<0.001). CONCLUSION: A combination of urinary calprotectin and clinical features could be useful for postoperative risk stratification of severe AKI in non-cardiac surgery patients.
Insight to Neglected Biomarkers in COVID-19: A Comprehensive Narrative Review".
Jalilian S, Bastani MN, Afsharzadeh F
Biomark Insights · 2026 · PMID 42256874 · Full text
In the context of COVID-19, a range of neglected biomarkers provide critical insights into the mechanisms of the disease and potential therapeutic targets. This review aims to address this gap by systematically analyzing...
In the context of COVID-19, a range of neglected biomarkers provide critical insights into the mechanisms of the disease and potential therapeutic targets. This review aims to address this gap by systematically analyzing the diagnostic and prognostic potential of these neglected biomarkers, with particular emphasis on their mechanistic connections to COVID-19 pathophysiology. Reduced levels of adiponectin and prostacyclin (PGI2) and elevated level of endothelin are associated with endothelial dysfunction, whereas elevated levels of endocan and endoglin are indicative of elevated vascular inflammation. Increased concentrations of markers such as angiopoietin, E-selectin, P-selectin, ICAM-1, and VCAM-1 suggest endothelial activation, while higher levels of fractalkine, galectin, HMGB1, and osteopontin reflect an ongoing inflammatory state. Immunological markers, including HMGB1, neopterin, and serum amyloid A, are significantly elevated, underscoring prolonged immune activation associated with severe COVID-19. Elevated levels of matrix metalloproteinases (MMPs) and soluble urokinase plasminogen activator receptor (SuPAR) highlight tissue remodeling and fibrinolytic imbalance related to vascular injury. Additionally, increases in soluble fms-like tyrosine kinase-1 (sFlt-1) and pentraxin reflect inflammatory pathways that exacerbate endothelial dysfunction. Elevated levels of syndecan-1 reflect endothelial glycocalyx degradation and impaired endothelial barrier integrity. Increased von Willebrand factor (vWF) indicates endothelial activation and injury with a prothrombotic shift. Elevated surfactant protein D (SP-D) is a marker of pulmonary epithelial injury and disruption of the alveolar-capillary interface. Other biomarkers, such as the receptor for advanced glycation end products (RAGE) and MR-proADM, signal oxidative stress and endothelial damage. Collectively, these biomarkers emphasize the extensive vascular and endothelial impairment in COVID-19, suggesting their utility as diagnostic tools and potential targets for therapeutic intervention against the systemic effects of the disease. This review advocates for the integration of these biomarkers into standard monitoring and treatment protocols for COVID-19, thereby enhancing personalized care. Furthermore, our analysis underscores the necessity for additional research into the roles of these biomarkers in other endothelial disorders, ultimately contributing to a more nuanced approach to managing viral infections characterized by vascular complications.
Bacterial Fluorescence-Based Biosensor for Detecting Propionate in Culture Media for Diagnostic Applications.
Fabela S, Martínez-Reyes CP, Arredondo-Hernandez R … +4 more , Castillo-Rojas G, Orduña P, Graue-Hernández EO, López-Vidal Y
Biomark Insights · 2026 · PMID 42211399 · Full text
BACKGROUND: Engineering bacteria for disease diagnosis and treatment is an emerging area of medical research that involves assessing short-lived molecules in complex, dynamic environments. Detecting metabolites offers s...
BACKGROUND: Engineering bacteria for disease diagnosis and treatment is an emerging area of medical research that involves assessing short-lived molecules in complex, dynamic environments. Detecting metabolites offers significant opportunities for identifying responsive cellular populations. Among suitable targets for this technology are short-chain fatty acids, such as propionate, that play crucial roles in human health and disease. OBJECTIVE: To develop a bacterial fluorescence-based biosensor capable of detecting propionate levels at the millimolar scale in low-volume samples across different culture media and optimize its application protocol. METHODS: Using strain BL21(DE3) transformed with the pPro24-GFP plasmid, which contains the green fluorescent protein () gene under the control of a propionate-inducible promoter, we achieved reliable propionate detection with a threshold of 10 mM in a small volume (750 μL). RESULTS: The fluorescence-based biosensor functioned in both Luria-Bertani and Dulbecco's modified Eagle media, producing fluorescence intensities of 3863 ± 957 arbitrary units. Validation using a portable Qubit 3.0 fluorometer yielded a receiver operating characteristic curve with a Cohen's kappa of 0.716, indicating substantial agreement. Proof-of-concept experiments using flow cytometry and mock fecal samples (healthy feces + 100 mM propionate) successfully detected the elevated propionate levels. CONCLUSION: This cost-effective, easy-to-use protocol provides a proof-of-concept for propionate detection in biological samples, with potential future applications in clinical diagnostics, particularly for gastrointestinal disorders in which propionate serves as a biomarker, where it could be used to monitor disease progression and therapeutic interventions.
Translating Liquid Biopsy into Practice- The Promise and Challenges of Circulating Tumor Cells in Ovarian and Lung Cancer Management.
Mustafa N, Tanisha MH, Tasneem F … +4 more , Siddique MA, Ahmed Z, Chowdhury NM, Rabbi F
Biomark Insights · 2026 · PMID 41971711 · Full text
The increasing mortality from ovarian and lung cancers worldwide is largely due to late diagnosis and therapeutic resistance. Conventional biomarkers such as CA125 and CYFRA 21-1 lack the sensitivity or the specificity f...
The increasing mortality from ovarian and lung cancers worldwide is largely due to late diagnosis and therapeutic resistance. Conventional biomarkers such as CA125 and CYFRA 21-1 lack the sensitivity or the specificity for monitoring real time disease progression or therapeutic response. This has prompted researchers to work on the development of relevant biomarkers that are minimally invasive for cancer diagnosis, prognosis and for therapeutic stratification. As such, liquid biopsies, which analyze tumor-derived components circulating in the blood including circulating tumor cells (CTCs), which are shed from primary or metastatic tumors into the bloodstream have emerged as a promising approach for detecting such cancers. This review critically analyzes the diagnostic and prognostic significance of CTCs in ovarian and lung cancers, highlighting technological advances, molecular characterization, and translational challenges associated with their clinical application. It briefly discusses the clinical utility of some biomarkers from liquid biopsies used in the diagnosis, prognosis as well as monitoring of ovarian and lung cancers with their detection methods. It highlights some of the relevant studies conducted in the field and finally it provides insights on the future of liquid biopsies. An extensive literature review analyzing papers between 2008 and 2026 was conducted using PubMed, Scopus, and Web of Science databases, that evaluated CTC detection methods, molecular profiling, and clinical outcomes in ovarian and lung cancer patients. Current literature reports that CTC enumeration and molecular characterization can provide significant insights into disease progression, therapeutic resistance and predict survival outcomes. Whilst the enrichment technologies such as CellSearch, ISET, and microfluidic platforms have enhanced detection sensitivity, variability in assay performance and lack of a clinical standardization impede proper implementation. CTCs represent a powerful liquid biopsy tool with potential to revolutionize cancer diagnostics and precision medicine. Integration of multi-omics profiling, CTC-derived organoids, and AI-driven analytical models may further enhance their clinical utility in guiding personalized treatment strategies for ovarian and lung cancer patients.
Circulating EMID2 as a Prognostic Biomarker of Poor Outcomes in Patients with Metastatic Colorectal Cancer.
Crespo-Bravo M, Syversen SR, Thorlacius-Ussing J … +5 more , Boisen MK, Liljefors M, Johansen JS, Karsdal MA, Willumsen N
Biomark Insights · 2026 · PMID 41948374 · Full text
BACKGROUND: EMID1 and EMID2 (also known as type XXVI collagen) are extracellular matrix (ECM) proteins that belong to the EDEN gene superfamily. Both proteins feature EMI domains, implicating them in protein-protein inte...
BACKGROUND: EMID1 and EMID2 (also known as type XXVI collagen) are extracellular matrix (ECM) proteins that belong to the EDEN gene superfamily. Both proteins feature EMI domains, implicating them in protein-protein interactions and ECM remodeling. Despite structural similarities EMID1 and EMID2 have distinct functions with EMID1 primarily expressed in epithelial cells and EMID2 in mesenchymal cells. Previous studies have shown that while EMID1 could promote metastasis EMID2 might inhibit tumor growth and dissemination. OBJECTIVES: Little is known about the specific functions and mechanisms of EMID1 and EMID2 in tumor development. Therefore, this study aims to explore the biomarker potential of EMID 1 and EMID2 in cancer. DESIGN: Retrospective study including a cross-sectional and a prognostic cohort to evaluate the biomarker potential of EMID1 and EMID2 in cancer. METHODS: We developed 2 competitive ELISAs targeting the N-terminal of EMID1 and EMID2. We compared EMID1 and EMID2 levels in serum from patients with different types of cancer (n = 216) to levels in healthy controls (n = 33). Thereafter, we measured EMID1 and EMID2 levels in a second cohort of patients with metastatic colorectal cancer (mCRC; n = 212) in stage IV treated with chemotherapy in combination with bevacizumab. RESULTS: The developed EMID1 and EMID2 ELISAs were specific, sensitive and robust. We did not find significant differences in EMID1 and EMID2 levels between patients with cancer and healthy controls, indicating limited diagnostic utility in cancer. However, in patients with mCRC, high EMID2 levels were associated with shorter PFS (241 days) compared to low levels (298 days) independently of other risk factors (HR = 1.57, 95% CI 1.04-2.36, = .031). Kaplan-Meier survival analysis showed no association between low or high levels of EMID1 or EMID2 and overall survival (OS). CONCLUSION: This study highlights EMID2 as prognostic biomarker in patients with mCRC, where higher levels correlated with more aggressive disease and shorter PFS. Future research should focus on elucidating the mechanisms underlying EMID2 degradation and its implications in cancer progression. Although EMID1 did not show diagnostic or prognostic value in this study, its biomarker potential in other types of cancer or benign diseases warrants further investigation.
Molecular Insights into the Regulatory Mechanisms Mediated by Hypoxia-Conditioned Skeletal Muscle Exosomal miRNAs.
Wang H, Shi B, Song W … +3 more , Lu L, Bajpai AK, Li Q
Biomark Insights · 2026 · PMID 41783906 · Full text
BACKGROUND: Hypoxia alters skeletal muscle metabolism and function through complex regulatory mechanisms, including exosome-mediated microRNA (miRNA) signaling. OBJECTIVES: This study profiled exosomal miRNAs from hypoxi...
BACKGROUND: Hypoxia alters skeletal muscle metabolism and function through complex regulatory mechanisms, including exosome-mediated microRNA (miRNA) signaling. OBJECTIVES: This study profiled exosomal miRNAs from hypoxic human skeletal muscle cells (HSMCs) to explore their roles in hypoxic adaptation. DESIGN: Human skeletal muscle cells were cultured under normoxic or hypoxic conditions, and secreted exosomes were isolated for comprehensive molecular profiling. High-throughput miRNA sequencing combined with integrative bioinformatic analyses was used to uncover hypoxia-responsive regulatory networks and key miRNA hubs involved in skeletal muscle adaptation. METHODS: HSMCs were cultured under normoxic or hypoxic conditions for 24 hours. Exosomes were isolated and characterized by transmission electron microscopy, nanoparticle tracking analysis, and immunoblotting. Exosomal miRNAs (n = 3 per group) were profiled using high-throughput sequencing, followed by differential expression, target prediction, enrichment, and network analyses. RESULTS: Isolated exosomes displayed typical morphology (mean size: 82.4 ± 3.2 nm) and expressed markers CD9, CD63, and TSG101. Seventy-four miRNAs were significantly dysregulated under hypoxia (23 upregulated, 51 downregulated; FDR < 0.05, |log2FC| ⩾ 1), including upregulated hsa-miR-210-3p and downregulated hsa-miR-486-5p, hsa-miR-127-3p, and hsa-miR-126-3p. Predicted targets (~2000 genes) included 451 genes differentially expressed in hypoxic versus normoxic skeletal muscle cells. Functional enrichment highlighted cancer-related, MAPK, PI3K-Akt, and HIF-1 signaling pathways, along with muscle differentiation processes. Network analysis identified hsa-miR-20a-5p as a central regulatory hub (46 targets), followed by hsa-miR-24-3p and hsa-miR-152-3p. hsa-miR-24-3p showed the strongest disease associations in the miRNA-disease network. CONCLUSIONS: Hypoxia induces distinct exosomal miRNA signatures in skeletal muscle, regulating genes involved in differentiation, migration, and stress response. These findings suggest that exosome-mediated miRNA signaling contributes to hypoxia-driven muscle adaptation and intercellular communication.
Galectin-3 Is Independently Associated With Short-Term Mortality and Identifies Low-Risk Patients With Acute Dyspnea in the Emergency Department: A Retrospective Cohort Study.
Zwawi A, Khoshnood AM, Ekelund U … +1 more , Wessman T
Biomark Insights · 2026 · PMID 41658332 · Full text
BACKGROUND: Dyspnea is a common and diagnostically challenging symptom in the emergency department (ED), particularly among older adults with multimorbidity. Traditional risk stratification tools often perform poorly in...
BACKGROUND: Dyspnea is a common and diagnostically challenging symptom in the emergency department (ED), particularly among older adults with multimorbidity. Traditional risk stratification tools often perform poorly in this population. Galectin-3 (Gal-3), a biomarker of inflammation and fibrosis, may reflect biological aging and resilience, potentially improving early mortality risk assessment. OBJECTIVES: To evaluate the independent association between Gal-3 and 30-day mortality in patients presenting with acute dyspnea; to assess its utility for identifying patients at low risk of short-term mortality; and to determine its incremental value in improving prediction of 30-day mortality when added to clinical risk models. DESIGN: Retrospective observational study based on the Acute Dyspnea Study (ADYS). METHODS: The study included 763 adult ED patients with acute dyspnea. Gal-3 was measured as NPX (Normalized Protein Expression) values using the Olink proximity extension assay, and NT-proBNP was measured using standard laboratory methods. The primary outcome was 30-day all-cause mortality. Multivariable logistic regression and Cox regression analyses were performed, with internal validation by bootstrap resampling. Predictive performance was evaluated using ROC curves, AUC, and the Youden index, and incremental value was assessed by AUC comparison and net reclassification improvement (NRI). RESULTS: Among the 763 patients, 49 (6.4%) died within 30 days. Gal-3 NPX was independently associated with 30-day mortality (OR 1.97; 95% CI: 1.16-3.36; p = 0.013). Although Gal-3 NPX alone demonstrated moderate discrimination (AUC 0.69), relatively low Gal-3 NPX levels within the cohort effectively ruled out short-term mortality, with a negative predictive value of 96%. Adding Gal-3 NPX to the clinical model modestly improved predictive performance (AUC increased from 0.803 to 0.819; NRI 0.028), primarily by enhancing identification of low-risk patients. CONCLUSION: Gal-3 NPX was independently associated with 30-day mortality in patients with acute dyspnea. Although its addition yielded only a modest, non-significant improvement in overall risk prediction, Gal-3 may be useful for ruling out short-term mortality, supporting its potential role as a negative prognostic marker in the ED setting.
Abnormal Serum Albumin, Alanine Aminotransferase, and Blood Urea Nitrogen are Associated with Higher Risks for Mechanical Ventilation and In-Hospital Mortality in COVID-19 Positive US Veterans.
Moss WD, Pires GR, Wei G … +6 more , Marquez JL, Sudduth JD, Miller AJ, Stoddard GJ, Agarwal JP, Jeyapalina S
Biomark Insights · 2026 · PMID 41567657 · Full text
BACKGROUND: Since the first reported case of Coronavirus Disease 2019 (COVID-19), clinicians and scientists have been challenged to contrive ideal prevention, detection, and treatment strategies. As the death toll surpas...
BACKGROUND: Since the first reported case of Coronavirus Disease 2019 (COVID-19), clinicians and scientists have been challenged to contrive ideal prevention, detection, and treatment strategies. As the death toll surpasses 1 million in the United States, identifying disease risk factors, specifically those risks related to severe disease manifesting as in-hospital mortality and invasive mechanical ventilation (MV), becomes crucial. OBJECTIVES: This study evaluated the association between abnormal blood biochemical markers, specifically albumin, alanine aminotransferase (ALT), creatinine, serum sodium, and blood urea nitrogen (BUN), to MV and in-hospital mortality in COVID-19 positive United States Veterans. DESIGN: We performed a retrospective cohort analysis on 298 760 US veterans admitted to any national Veterans Affairs Hospital (VHA) with a positive COVID-19 test from March 1, 2020, to August 31, 2021, resulting in a total of 30 729 patients. METHODS: A selection of patient-specific and COVID-19 test-related data was collected from the COVID-19 Shared Data Resources sourced from the VHA's Corporate Data Warehouse. These data were statistically analyzed using multivariable Cox regression models. RESULTS: Patients with lower albumin (<3.5 g/L); and higher BUN (>23 mg/dL), creatinine (>1.5 mg/dL), and ALT (>40 U/L) levels had increased risks for MV (29%, 40%, 20%, 26%) and in-hospital mortality (46%, 69%, 23%, 13%), respectively. Interestingly, patients with lower BUN (<11 mg/dL) values had decreased risks for both MV (22%) and in-hospital mortality (31%). Patients with sodium <135 mmol/L had an increased risk for MV and in-hospital mortality (30%, 9%), while sodium >145 mmol/L had an increased risk for in-hospital mortality (125%). CONCLUSION: Overall, veterans hospitalized with COVID-19 and having abnormal albumin, ALT, BUN, and creatinine values were statistically associated with ventilatory status and case-fatality.
Salivary Proteomics & Gene Expression Analysis: Applications in Orthodontics and Oral Health Care Research-A Pilot Project.
Gandhi V, Chen PJ, Yadav S
Biomark Insights · 2025 · PMID 41262076 · Full text
BACKGROUND: Advances in analytical techniques, including salivary proteomics and gene expression analysis, have enabled the identification of thousands of proteins and specific genetic markers, providing a comprehensive...
BACKGROUND: Advances in analytical techniques, including salivary proteomics and gene expression analysis, have enabled the identification of thousands of proteins and specific genetic markers, providing a comprehensive understanding of salivary composition and its dynamic changes in response to therapeutic interventions. OBJECTIVES: To conduct the salivary proteomic analyses using the LC-MS/MS method and identify the number of proteins in the whole saliva. This study also assessed the effect of an intraoral vibration device on the expression of specific genes associated with the bone remodeling process. DESIGN: This pilot project is a prospective study where salivary samples were assessed at baseline (0 day), Midpoint (15 days), and Endpoint (30 days) following the intervention. METHODS: This study utilized an intraoral vibration device as a therapeutic intervention to observe the changes in the salivary proteomic analyses using the LC-MS/MS method. Salivary gene expression analysis was conducted for ALPL, OPN, IL1B, IL1RN, IL1R1, TNF alpha, RANKL, and RUNX2 genes. RESULTS: A total of 1119 proteins in 1059 clusters at 1 minimum peptide and a 444 proteins in 384 clusters at 2 minimum peptides were identified in saliva. Out of all of the genes included in this experiment, OPN showed significant upward change at mid point (9 fold) (15 days) followed by moving toward the baseline level (2.3-fold) toward the end point (30 days). CONCLUSION: This study highlights the potential of salivary proteomics and gene expression analysis as a promising tool for biomarker discovery, emphasizing the complexity and their variability. Despite of some challenges, the advantages of whole saliva collection and the sensitivity of shotgun proteomics and gene expression analysis support its potential as a high-throughput, practical approach for future applications in the field of oral health care.
The Additional Prognostic Value of Serial Biomarker Measurements for Extubation Failure Among Patients With COVID-19 Acute Respiratory Distress Syndrome.
Groenland CNL, Siemers AH, Dubois EA … +5 more , Gommers D, Heunks L, Wils EJ, Baggen VJM, Endeman H
Biomark Insights · 2025 · PMID 41245882 · Full text
BACKGROUND: Extubation failure is associated with adverse outcomes in critically ill patients. While single biomarker measurements can aid prediction, repeated biomarker measurements can help to timely recognize underlyi...
BACKGROUND: Extubation failure is associated with adverse outcomes in critically ill patients. While single biomarker measurements can aid prediction, repeated biomarker measurements can help to timely recognize underlying diseases. OBJECTIVES: The aim of this study was to investigate the temporal evolution of cardiac (N-terminal pro-B-type natriuretic peptide [NT-proBNP], high-sensitivity troponin T [Hs-TnT]) and inflammatory biomarkers (interleukin-6 [IL-6] and procalcitonin [PCT]) prior to extubation and determine their additional prognostic value. DESIGN: Retrospective cohort study. METHODS: Patients with COVID-19 extubated after mechanical ventilation were included. Daily biomarker levels were collected up to 3 days before extubation. The primary endpoint was extubation failure, defined as reintubation or death within 7 days. Linear mixed-effect models were used to analyze biomarker trajectories in patients with extubation success and failure. Each day before extubation a logistic regression model (consisting of the 4 biomarkers) was constructed to determine the model with the best discriminative ability. RESULTS: Among 297 patients, 21.5% experienced extubation failure. Log Hs-TnT, NT-proBNP and PCT were higher on all days in patients with extubation failure ( < .001, = .01, = .01, respectively), whereas log IL-6 was not ( = .54). There was no difference in the change of biomarkers over the days between patients with extubation success and failure (-value for interaction = .11, = .82, = .31, = .84, respectively). The performance of the logistic regression model including the 4 biomarkers on the day of extubation was significantly better than the model 3 days before extubation (AUC 0.71, 95% CI: 0.64-0.79 vs AUC 0.66, 95% CI: 0.58-0.73, = .03). CONCLUSION: Hs-TnT, NT-proBNP and PCT measured on the days before extubation are consistently higher in patients with extubation failure. However, there was no relation between the change in biomarker levels over time and extubation outcome. The serial assessment of Hs-TnT, NT-proBNP, PCT, and IL-6 do not seem to add prognostic information to predict extubation failure.
Exploring Sex-Related Difference in Cerebrospinal Fluid/Blood Quotient of Albumin in Older Patients Undergoing Hip Fracture Surgery: Insight From the ORTODEL and BIODEL Study.
Castellazzi M, Ferrara MC, Arosio B … +7 more , Lozano-Vicario L, Pinardi E, Ornago AM, Okoye C, Martínez-Velilla N, Bellelli G, Volpato S
Biomark Insights · 2025 · PMID 41210261 · Full text
BACKGROUND: The blood-cerebrospinal fluid barrier (BCSFB) regulates substance exchange between the blood and cerebrospinal fluid (CSF). OBJECTIVES: This study investigated sex-related differences in the CSF/blood quotien...
BACKGROUND: The blood-cerebrospinal fluid barrier (BCSFB) regulates substance exchange between the blood and cerebrospinal fluid (CSF). OBJECTIVES: This study investigated sex-related differences in the CSF/blood quotient of albumin (QAlb), a BCSFB function biomarker, in older patients undergoing spinal anesthesia for hip fracture (HF) surgery. DESIGN: Seventy-eight patients aged ⩾65 years (18 males, 60 females) undergoing HF repair were enrolled. METHODS: Baseline variables, including age, sex, diagnosis of dementia, were collected. The BCSFB function was assessed using the CSF/blood quotient of albumin (QAlb). RESULTS: Dementia prevalence was similar in men (22.2%) and women (17.6%), as was postoperative delirium (POD) (men 27.8%, women 33.3%). Despite similar demographics, men exhibited significantly higher CSF albumin concentrations ( = .031) and QAlb values ( = .023) compared to women. No differences were found in QAlb value between patients with or without dementia in male ( = .645) and female ( = .102) subgroups. Moreover, no differences in QAlb value emerged between those with or without POD in males ( = .173) and females ( = .225). CONCLUSION: Despite sample size and sex imbalance, our analyses highlight a sex-related discrepancy in BCSFB function in older patients underscoring the need for sex-specific QAlb reference ranges. Normalization of QAlb values by sex may be essential to prevent over- or underestimation of BCSFB dysfunction in the 2 sexes. Future studies with larger, balanced cohorts may clarify these differences.
Advancing Clinical Use of Neurofilament Light Chain: Translational Insights From Research to Routine Practice.
La Civita E, Nicolella V, Fiorenza M … +5 more , Cosimato V, Castaldo G, Morra VB, Moccia M, Terracciano D
Biomark Insights · 2025 · PMID 41180593 · Full text
Neurofilament Light Chain (NfL) has emerged as a promising biomarker for neurological diseases. NfL, a structural component of axons, is released into cerebrospinal fluid (CSF) and blood following neuro-axonal damage. Hi...
Neurofilament Light Chain (NfL) has emerged as a promising biomarker for neurological diseases. NfL, a structural component of axons, is released into cerebrospinal fluid (CSF) and blood following neuro-axonal damage. Highly sensitive immunometric assays have enabled its reliable quantification in blood, facilitating non-invasive monitoring. Several studies demonstrated strong correlations between NfL levels and the risk of developing different neurological diseases and, in individuals already living with a neurological disease, with the risk of worsening. However, interpretation is affected by factors like age, BMI, renal function, and comorbidities. NfL is already utilized as a diagnostic and prognostic biomarker in clinical practice, particularly in specialized centers and research settings, although no FDA-cleared assay is currently available for routine use. Recent research has highlighted that NfL may represent the first of a new generation of neurological biomarkers, with many more ready to come, such as glial fibrillary acidic protein (GFAP), further improving diagnostic and prognostic accuracy. Despite its promising role in the landscape of biomarkers, challenges remain to implement NfL in daily clinical practice, including standardization of assays, defining reference values, and ensuring methodological consistency. Addressing these limitations will be essential for integrating NfL into routine clinical practice, ultimately advancing precision medicine in neurology.
Extracellular Vesicle-Derived miRNAs as Diagnostic Biomarkers for Pancreatic Ductal Adenocarcinoma: A Systematic Review of Methodological Rigour and Clinical Applicability.
Patel RD, Patel B, Crnogorac-Jurcevic T
Biomark Insights · 2025 · PMID 41180592 · Full text
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with currently limited early detection options. Extracellular vesicle (EV)-derived microRNAs (miRNAs) have gained interest as non-invasive...
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with currently limited early detection options. Extracellular vesicle (EV)-derived microRNAs (miRNAs) have gained interest as non-invasive diagnostic biomarkers due to their stability in circulation and tumour-specific profiles. However, the methodological robustness of existing literature remains unclear. OBJECTIVES: To systematically evaluate the diagnostic accuracy and methodological quality of studies investigating EV-derived miRNAs for PDAC detection, with a particular focus on adherence to established EV characterisation guidelines. DESIGN: Systematic review registered with PROSPERO (CRD42024501503) and conducted in accordance with PRISMA 2020 reporting standards. METHODS: We searched PubMed, EMBASE, Medline and Cochrane for original human studies published up to February 1, 2025, evaluating EV-derived miRNAs in biofluids from PDAC patients. Eligible studies reported diagnostic accuracy metrics (sensitivity, specificity, Area Under the Curve (AUC)). Methodological quality was assessed using the QUADAS-2 tool, and EV validation was scored against the Minimal Information for Studies of Extracellular Vesicles 2018 (MISEV) 2018 checklist (updated 2023). RESULTS: Fifty-six studies were included. Plasma and serum were the most commonly used biofluids. The most frequently evaluated individual miRNAs were miR-21 (13 studies), miR-10b (9 studies), and miR-451a (7 studies). Although several studies reported high diagnostic performance (AUCs up to 0.99), MISEV adherence was limited: only 23.1% of miR-21 studies demonstrated strong EV validation, and >70% of all studies lacked EV quantification or protein marker analysis. Multi-miRNA panels achieved higher AUCs (often > 0.85) but typically scored poorly on EV characterisation. Only 2 of 56 studies included external validation, and 54 studies lacked blinding, contributing to substantial risk of bias. CONCLUSION: EV-derived miRNAs are promising PDAC biomarkers, but progress is hindered by inconsistent methods, poor EV validation, and minimal external verification. Translation to clinical use requires robust EV characterisation, standardised workflows, and prospective multi-cohort studies.
Latent Intrarenal Renin-Angiotensin-Aldosterone System Activation Could Persist Until Early School-Aged in Children with a History of Low Birth Weight.
Ishimori S, Ishiko S, Fujimura J … +11 more , Aoyama S, Kimura Y, Kitakado H, Ueda C, Inoki Y, Tanaka Y, Horinouchi T, Yamamura T, Sakakibara N, Nagano C, Nozu K
Biomark Insights · 2025 · PMID 41180591 · Full text
BACKGROUND: The renin-angiotensin-aldosterone system (RAAS) plays a crucial role in kidney development and the progression of chronic kidney disease (CKD). OBJECTIVES: To identify children with low birth weight (LBW) at...
BACKGROUND: The renin-angiotensin-aldosterone system (RAAS) plays a crucial role in kidney development and the progression of chronic kidney disease (CKD). OBJECTIVES: To identify children with low birth weight (LBW) at risk of CKD who have RAAS activation. DESIGN: We conducted a prospective cohort study to evaluate whether a history of LBW contributes to the development of latent RAAS activation using urine samples from patients with short stature with no clinical kidney symptoms. Additionally, among children who had idiopathic nephrotic syndrome (INS), we examined how a history of LBW contributes to the development of latent RAAS activation using residual kidney biopsy samples. METHODS: We prospectively evaluated angiotensinogen (AGT) using spot urine in children with and without a history of LBW, who required evaluation for short stature without kidney symptoms at registration. We also performed immunohistochemical staining of AGT using kidney biopsy specimens of subjects with and without a history of LBW who had INS. Urinary AGT was assessed as a marker of intrarenal RAAS. RESULTS: In 45 children (median age 5 years), urinary AGT/creatinine (Cr) levels were significantly higher in children with a history of LBW (n = 24) than in those without (n = 21, median: 12.6 vs 6.7 µg/g･Cr, mean: 15.4 vs 9.1 µg/g･Cr, < .01). The unadjusted mean difference between the 2 groups and the 95% confidence interval were 6.3 and (1.6, 11.1), respectively. In the immunohistochemical kidney pathological study, the positive area of AGT staining in the kidney tubules of 3 subjects with a history of LBW was more extensive than that of 3 additional subjects without a history of LBW. CONCLUSION: Our results indicated that latent intrarenal RAAS activation in children with a history of LBW persists until early school age and may contribute to the progression of CKD.
CXCL10 (IP-10) and anti-ZnT8 autoantibodies: Exploratory indicators of risk in pancreatic transplant rejection.
Jäätma M, Murruste M, Kase K … +3 more , Metsküla K, Uibo R, Vorobjova T
Biomark Insights · 2025 · PMID 41133256 · Full text
BACKGROUND: Measurement of chemokine CXCL10 is a novel approach to assess the transplant rejection risk and to detect the rejection. While CXCL10 has shown itself to be useful in renal transplants, there are only a few s...
BACKGROUND: Measurement of chemokine CXCL10 is a novel approach to assess the transplant rejection risk and to detect the rejection. While CXCL10 has shown itself to be useful in renal transplants, there are only a few studies on the association between pancreas transplantation and CXCL10. Furthermore, the importance of autoantibodies associated with type I diabetes in pancreas transplantation are relatively poorly understood. OBJECTIVES: To determine whether there is an association between CXCL10 plasma levels and graft rejection in simultaneous pancreas and kidney transplant recipients, and to assess the effects of pancreas autoantibodies on pancreatic transplant rejection. DESIGN: A retrospective case-control study was conducted. METHODS: In total of 23 individuals (11 male and 12 female, mean age 39.5 (SD ± 7.6) years) who underwent simultaneous pancreas and kidney transplantation, and in 8 healthy controls (evenly distributed in terms of gender, mean age 26.1 (SD ± 1.5) years) plasma samples were analyzed for CXCL10 and autoantibody levels using ELISA. The data was categorized into preoperative, perioperative and postoperative samples and were further juxtaposed in relation to rejection episodes. RESULTS: Preoperative CXCL10 levels did not differ from those for healthy individuals, but they rose postoperatively ( = .02). The median preoperative plasma concentration of CXCL10 was 68 pg/ml and increased to 123 pg/ml postoperatively. A postoperative plasma CXCL10 cut-off value of 297 pg/ml was indicative of rejection. Postoperative autoantibodies were detected in 10 recipients, 4 of whom were positive for anti-ZnT8 autoantibodies, and 2 were positive for more than 1 type autoantibody. All recipients who were positive for anti-ZnT8 autoantibodies or for more than 1 type autoantibody experienced rejection. CONCLUSION: Elevated CXCL10 levels during the first 3 months after transplantation seem to be a risk factor for rejection. The post transplant presence of anti-ZnT8 autoantibodies was associated with transplant rejection.
Blood Based Vascular Marker Responses to Ocufolin in Diabetic Retinopathy Patients Carrying MTHFR Polymorphisms.
Wang J, Hoover A, Townsend JH … +4 more , Yehoshua Z, Stremousov K, de Rivero Vaccari JP, Jiang H
Biomark Insights · 2025 · PMID 41020092 · Full text
BACKGROUND: Patients with inborn errors of metabolism related to Methylenetetrahydrofolate reductase () gene variants are at an increased risk for microvascular complications resulting from diabetic retinopathy. Early in...
BACKGROUND: Patients with inborn errors of metabolism related to Methylenetetrahydrofolate reductase () gene variants are at an increased risk for microvascular complications resulting from diabetic retinopathy. Early intervention with targeted nutritional support, particularly folate supplementation, may help stabilize metabolic function and slow the progression of diseases such as diabetes and hypertension, especially before irreversible structural damage occurs. OBJECTIVES: To assess the effects of the folate supplement Ocufolin on serum markers in patients with Type 2 diabetes (T2D) and mild diabetic retinopathy (MDR). DESIGN: Prospective Cohort Study. METHODS: Ten patients with both MDR and polymorphisms () were enrolled in the present study and received Ocufolin to address errors in folate methylation metabolism. Patients were excluded if they had a history of other ocular or systemic diseases. Serum biomarkers associated with clinical chemistry (homocysteine, high-sensitivity C-reactive protein [hs-CRP], myeloperoxidase [MPO], fasting insulin, triglycerides, total cholesterol, high density lipoprotein [HDL], low density lipoprotein [LDL], Oxidized-LDL [Ox-LDL], vascular endothelial growth factor [VEGF], D-Dimer, hemoglobin A1c [HbA1c] and glutathione) were measured pre-and post-intervention. RESULT: Treatment with Ocufolin resulted in a 23% decrease in serum homocysteine ( = .005), an 18% decrease in hsCRP, a 13% decrease in fasting insulin, a 15% increase in D-Dimer ( = .03) and a 47% decrease in VEGF ( = .04). Additionally, there was a 9% increase in glutathione, a 2% increase in MPO, a 6% reduction in triglycerides, a 3% increase in total cholesterol, a 4% increase in HDL, a 4% increase in LDL, an 8% increase in Ox-LDL. HbA1c did not change. CONCLUSION: Normalizing folate metabolism through Ocufolin significantly improved key blood-based biomarkers in patients with diabetic retinopathy. These metabolic improvements may underlie enhanced retinal perfusion and reduced oxidative stress, suggesting potential adjunctive therapeutic benefits for managing vascular retinopathies in this population.
Circulating Biomarkers and Recurrence of Persistent Atrial Fibrillation After Electrical Cardioversion.
Andersen EL, Solberg MG, Enger S … +9 more , Onarheim S, Olufsen M, Berge T, Åkra S, Kleveland MK, Christophersen IE, Ulimoen SR, Seljeflot I, Tveit A
Biomark Insights · 2025 · PMID 40949791 · Full text
BACKGROUND: Rhythm control therapy is recommended for individuals with symptomatic atrial fibrillation (AF) to reduce symptoms and improve quality of life. Electrical cardioversion (ECV) is used to restore sinus rhythm (...
BACKGROUND: Rhythm control therapy is recommended for individuals with symptomatic atrial fibrillation (AF) to reduce symptoms and improve quality of life. Electrical cardioversion (ECV) is used to restore sinus rhythm (SR), but AF recurrence is common. OBJECTIVE: We aimed to investigate if a selection of circulating biomarkers can predict rhythm outcomes in individuals with persistent AF treated with ECV. DESIGN: This was an observational cohort study. METHODS: We included 200 individuals aged ⩾ 18 years referred for ECV of AF from November 2017 to March 2022. We obtained blood samples 0 to 6 weeks before ECV. Plasminogen activator inhibitor type 1 (PAI-1) activity, soluble suppression of tumorigenicity 2 (sST2), galectin-3 (GAL-3), interleukin-6 (IL-6), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), growth differentiation factor-15, (GDF-15), transforming growth factor-β-1 (TGF-β1), and fibroblast growth factor-23 (FGF-23) were analyzed by ELISA methods. The participants recorded thumb ECGs twice daily for 28 days after the ECV to detect AF recurrence. RESULTS: A total of 188 individuals were eligible for the analyses. Twenty-four participants converted spontaneously to SR before ECV. Among the cardioverted, 74 maintained SR, whereas 90 experienced AF recurrence before hospital discharge (n = 15) or during the follow-up period of 28 days (n = 75). TIMP-1 was significantly higher in those with AF recurrence than in those who maintained SR, but overlapping distributions suggest limited predictive ability. PAI-1 activity, sST2, GAL-3, IL-6, MMP-9, GDF-15, TGF-β1, and FGF-23 did not differ among the participants who had ECV. CONCLUSION: TIMP-1 was higher in participants with recurrence of AF after ECV, but its predictive ability was limited. None of the other biomarkers were associated with AF recurrence. We do not recommend using these biomarkers for candidate selection for ECV of persistent AF.
Pre-treatment Circulating Tumor Cell Associated White Blood Cell Clusters Independently Predict Poor Survival in Patients with Extensive-disease Small Cell Lung Cancer.
Wang Y, Zhang M, Chen C … +10 more , Liu Y, Gao Y, Li H, Lu B, Hu M, Zhang H, Lin PP, Ren Z, Zhang T, Xu S
Biomark Insights · 2025 · PMID 40787208 · Full text
BACKGROUND: Patients with extensive disease (ED)-small cell lung cancer (SCLC) commonly suffer a more inferior prognosis than those with limited disease (LD)-SCLC. OBJECTIVES: This study aims to investigate the heterogen...
BACKGROUND: Patients with extensive disease (ED)-small cell lung cancer (SCLC) commonly suffer a more inferior prognosis than those with limited disease (LD)-SCLC. OBJECTIVES: This study aims to investigate the heterogeneity and prognostic significance of various aneuploid circulating tumor cells (CTCs) subtypes and CTC-associated white blood cell (CTC-WBC) clusters in patients with LD-and ED-SCLC respectively. DESIGN: This prospective, non-interventional, single-center study included 48 patients with LD-SCLC and 47 patients with ED-SCLC. METHODS: A total of 95 SCLC patients were prospectively enrolled and serial blood samples were obtained before chemotherapy administration (t) and after 2 cycles of chemotherapy (t). Comprehensive in situ co-detection of CTCs and CTC-WBC clusters were performed in all enrolled patients. RESULTS: The analysis revealed no significant difference in CTCs quantity between LD-SCLC and ED-SCLC patients ( = .610). However, significant morphologic heterogeneity in CTCs, including cell size and chromosome 8 (Chr8) ploidy in CTCs was observed between the 2 groups ( < .001 and < .001). Patients with post-therapeutic small cell CTCs ⩾ 2/6 ml or triploid CTCs ⩾ 2/6 ml exhibited reduced overall survival (OS) compared to those with small cell CTCs < 2/6 ml or triploid CTCs < 2/6 ml in the ED-SCLC ( = .011 and = .018). Additionally, the positive detection of post-therapeutic tetraploid CTCs was associated with inferior survival in both LD-and ED-SCLC ( = .041 and = .049). The presence of CTC-WBC clusters at baseline and after treatment significantly correlated with inferior OS in ED-SCLC ( = .016 and = .028) but not in LD-SCLC ( = .355 and = .621). Multivariate analysis identified brain metastasis and pre-treatment CTC-WBC clusters as independent prognostic factors for OS in ED-SCLC patients ( = .004 and = .013). CONCLUSION: Ideal biomarkers should be more specific for survival prediction in patients with different disease stages. Pre-treatment CTC-WBC clusters can independently predict inferior OS in ED-SCLC but not LD-SCLC.
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