Journal of Circulating Biomarkers最新文献

{"title":"Biomarkers and their association with cognitive impairment in patients with chronic heart failure: a systematic review and meta-analysis.","authors":"Marina Bustamante Ordoñez, Eduardo Marchand Bayona, José Rondón Gonzales, Carlos Zavaleta-Corvera, Gino Vasquez-Paredes","doi":"10.33393/jcb.2026.3682","DOIUrl":"https://doi.org/10.33393/jcb.2026.3682","url":null,"abstract":"<p><strong>Introduction: </strong>The aim was to synthesize the evidence on the association between circulating biomarkers and Cognitive Impairment (CI) in patients with Chronic Heart Failure (CHF), and to assess methodological quality and certainty of evidence.</p><p><strong>Methods: </strong>Systematic review and meta-analysis conducted under PRISMA 2020 (PROSPERO CRD42024626152). Searches were performed in PubMed/MEDLINE, Scopus, Web of Science, and Embase up to April 30, 2025. Observational studies and clinical trials that measured cardiac or extracardiac biomarkers in patients with HF and evaluated CI using validated tools were included. Mean differences (MD) were calculated using random-effects models (DerSimonian-Laird). Methodological quality was assessed with the Newcastle-Ottawa Scale (NOS) and certainty of evidence with the GRADE approach.</p><p><strong>Results: </strong>Seven studies met the inclusion criteria. Patients with CHF and CI had significantly higher levels of high-sensitivity troponin T (hs-cTnT) compared to those without CI (MD 3.36 ng/L; 95% CI 0.42-6.31; p = 0.03; I² = 0%). In contrast, NT-proBNP showed a non-significant trend (MD 410.16 pg/mL; 95% CI -276.22-1096.53; p = 0.24; I² = 51%). Methodological quality was moderate (median NOS 7/9). Extracardiac biomarkers such as GDF-15, S100B, pTau, NfL, BDNF, and sICAM-1/sVCAM-1 were associated with inflammation, endothelial dysfunction, and neurodegeneration. With GRADE, overall certainty was very low for both biomarkers due to observational design, imprecision, and heterogeneity.</p><p><strong>Conclusions: </strong>hs-cTnT is consistently associated with CI in HF, whereas NT-proBNP does not show a robust relationship. Extracardiac biomarkers may provide complementary information in cognitive stratification, although their clinical application requires validation in multicenter longitudinal cohorts with analytical and neuropsychological standardization.</p>","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":"15 ","pages":"78-89"},"PeriodicalIF":0.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13655607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149185030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating free and low-density lipoprotein-bound GD2 can compete <i>in vitro</i> with neuroblastoma cells for binding therapeutic anti-GD2 antibodies.","authors":"Christina S Turn, Christine M Busch, Cara Toland, Hamid Bassiri, Michael D Hogarty, Frank M Balis","doi":"10.33393/jcb.2026.3797","DOIUrl":"10.33393/jcb.2026.3797","url":null,"abstract":"<p><strong>Introduction: </strong>GD2 is a ganglioside expressed on neuroblastoma cell membranes and shed into the circulation, where it primarily circulates bound to low-density lipoprotein (LDL). We questioned whether LDL-bound GD2 could interfere with the binding of therapeutic anti-GD2 monoclonal antibodies (like dinutuximab) to neuroblastoma cells.</p><p><strong>Methods: </strong>The GD2-expressing neuroblastoma cell line IMR5 was stained with an anti-GD2 antibody tagged with allophycocyanin (APC) at the lowest possible saturating concentration, and mean fluorescence intensity was measured by flow cytometry after <i>in vitro</i> exposure to GD2-LDL or free GD2 at multiple concentrations. Control experiments assessed the ability of GD2-expressing and GD2-non-expressing cells to compete for anti-GD2-APC antibodies with IMR5 cells.</p><p><strong>Results: </strong>Free and LDL-bound GD2 reduced anti-GD2-APC antibodies' binding to IMR5 cells <i>in vitro</i> in a concentration-dependent manner. At physiologically relevant concentrations, LDL-bound GD2 blocked antibody binding to IMR5 to a greater extent than free GD2, including at 100 nM, a concentration below median GD2 concentrations in patients with high-risk neuroblastoma. At higher concentrations, LDL-bound GD2 inhibited antibody binding to IMR5 by up to 92.6%, whereas the same concentration of free GD2 only decreased antibody binding by 56.6.</p><p><strong>Conclusions: </strong>At concentrations found in patients with high-risk neuroblastoma, both free GD2 and LDL-bound GD2 blocked anti-GD2 antibody binding to neuroblastoma cells. These data suggest that circulating GD2-LDL could impact the efficacy of therapeutic anti-GD2 antibodies administered to patients with a high disease burden during induction therapy or at relapse and may have therapeutic implications for GD2-directed adoptive cellular therapies.</p>","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":"15 ","pages":"69-77"},"PeriodicalIF":0.0,"publicationDate":"2026-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13594967/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149025612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relevance of existing blood-based biomarkers for detection of hepatocellular carcinoma: a prospective case-control study.","authors":"Mohammed Farouk, Kunkumabalasubramanian Sreedurgalakshmi, Jeyanthi Rebecca","doi":"10.33393/jcb.2026.3774","DOIUrl":"10.33393/jcb.2026.3774","url":null,"abstract":"<p><strong>Introduction: </strong>This study evaluated the diagnostic performance of conventional blood-based biomarkers for detecting hepatocellular carcinoma (HCC) in patients with chronic liver disease (CLD).</p><p><strong>Methods: </strong>In this prospective case-control study, adults with CLD (with and without HCC) underwent blood sampling for alpha-fetoprotein (AFP), des-gamma-carboxy prothrombin (DCP), and cell-free DNA (cfDNA). Diagnostic performance was assessed individually and in combination using regression analyses, with radiological imaging as the reference standard. Pre- and post-treatment biomarker levels were analyzed in a subset of HCC patients.</p><p><strong>Results: </strong>Among 453 analyzed participants (131 HCC, 322 non-HCC controls), AUROCs for AFP, DCP, and cfDNA were 0.84, 0.76, and 0.64, respectively. At Youden index-derived thresholds, sensitivities were 62% for AFP, 65% for DCP, and 59% for cfDNA, with corresponding specificities of 93%, 74%, and 64%. Combining biomarkers via regression models did not improve diagnostic performance. AFP demonstrated poor sensitivity (32%) for early-stage HCC detection, and performance varied by disease etiology. Among treatment response markers, DCP showed superior potential.</p><p><strong>Conclusion: </strong>In a real-world CLD cohort, conventional blood-based biomarkers demonstrate limited sensitivity for early-stage HCC detection. These findings highlight the need for molecular and genetic approaches to improve early HCC diagnosis.</p>","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":"15 ","pages":"58-68"},"PeriodicalIF":0.0,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13592045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149018182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating miRNAs (135a-5p, 646 AND 1271-5P) in Breast Cancer Diagnosis and Staging: Integrative Network and Functional Analysis.","authors":"Asmaa R Abdel-Hamed, Marina Barsom, Mahmoud M Kamel, Dina M Abo-Elmatty, Abdullah Ay Gibriel","doi":"10.33393/jcb.2026.3840","DOIUrl":"https://doi.org/10.33393/jcb.2026.3840","url":null,"abstract":"<p><strong>Introduction: </strong>Breast cancer (BC) remains a leading cause of cancer-related mortality among women worldwide. Despite advances in molecular diagnostics, reliable non-invasive biomarkers for early detection and disease staging remain limited. Circulating microRNAs (miRNAs) are promising epigenetic regulators involved in tumor development and progression.</p><p><strong>Methods: </strong>Determination of plasma miRNA (1271-5p, miR-646, and miR-135a-5p) differential expression profiles in an Egyptian cohort comprising 111 BC patients (stages 0-IV), 25 benign breast disease cases, and 24 healthy controls. Their diagnostic and stage-specific performance was assessed alongside integrative analyses of predicted and validated biological targets with network construction.</p><p><strong>Results: </strong>miR-1271-5p was downregulated in benign tumors but overexpressed across all BC stages. miR-646 was generally downregulated, with a notable increase in stage III, whereas miR-135a-5p was elevated in benign and early-stage disease before declining in metastatic stage IV. ROC analyses demonstrated strong discriminatory performance, with miR-1271-5p distinguishing early-stage BC from controls and benign lesions, miR-646 separating benign/early malignant cases from controls, and miR-135a-5p identifying metastatic disease. Combined miRNA panels improved discrimination between malignant and non-malignant samples and between early and advanced stages. Integrative analyses identified putative regulation of ZEB1, CCND2, FOXN3, and RUNX2, while TP53TG1, ZFAS1, XIST, and MALAT1 emerged as potential interaction hubs. Functional enrichment suggested involvement in AMPK, FOXO, SUMOylation, TP53-mediated, and immune-related pathways.</p><p><strong>Conclusions: </strong>Circulating miR-1271-5p, miR-646, and miR-135a-5p, individually and in combination, show promise as non-invasive diagnostic and stage-specific biomarkers for BC. Integrative network analyses provide insight into their putative roles in BC progression.</p>","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":"15 ","pages":"47-57"},"PeriodicalIF":0.0,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13579154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148991806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From glycosylation to inflammation: insights from NMR-Derived GlycA and GlycB.","authors":"Dalia Ahmed, Karla Christina Sousa Silva, Mariet Wium, Luiz Fernando Zerbini, Stefano Cacciatore","doi":"10.33393/jcb.2026.3772","DOIUrl":"10.33393/jcb.2026.3772","url":null,"abstract":"<p><p>Post-translational modifications (PTMs) play a crucial role in increasing proteomic diversity. N-linked glycosylation acts as a key regulatory layer that influences protein stability, trafficking, circulation, and immune responses. Unlike conventional inflammatory biomarkers that measure individual proteins, nuclear magnetic resonance (NMR) spectroscopy identifies the combined signals GlycA and GlycB from glycoproteins, offering an overall view of systemic glycoprotein changes. These signals represent the N-glycosylation patterns of several abundant acute-phase proteins (APPs), giving detailed molecular insights. This review offers a detailed assessment of GlycA and GlycB as mechanistically grounded indicators of liver glycoprotein remodeling and systemic inflammation. GlycA mainly indicates the levels and structural complexity of N-acetylglucosamine (GlcNAc) and N-acetylgalactosamine (GalNAc) residues linked to acute-phase glycoproteins and glycan branching. In contrast, GlycB reflects changes in terminal sialylation, which influences glycoprotein half-life, immune recognition via lectins, and inflammatory signaling. Collectively, these biomarkers combine measurements of hepatic APP production with variations in glycan structure, offering mechanistically anchored reporters of hepatic glycoprotein remodeling. We explore the enzymatic pathways responsible for N-glycan branching, fucosylation, and sialylation, as well as the roles of major APP scaffolds in the GlycA and GlycB resonances. We also highlight the emerging clinical significance of these signals across infectious, autoimmune, cardiovascular, metabolic, neurodegenerative, and cancer-related diseases. Rather than serving simply as markers of inflammation, GlycA and GlycB provide mechanistically interpretable readouts of cytokine-driven hepatic glycoprotein remodeling and systemic immune activation, supporting their application in disease risk stratification, longitudinal monitoring, therapeutic response assessment, and precision medicine.</p>","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":"15 ","pages":"38-46"},"PeriodicalIF":0.0,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13564094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148956620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"VEGF, TNF-α, and PCT efficiency for traumatic brain injury prognosis evaluation in the first 72 h.","authors":"Diya Hasan, Ola M Al-Sanabra, Mutaz Jamal Al-Khreisat, Ghaith H Mansour, Tareq Nayef AlRamadneh, Moath Alqaraleh, Alqassem H Abuarqoub, Ahmad Al Tibi, Mu'ad Al-Zu'abe, Sara Abaza","doi":"10.33393/jcb.2026.3633","DOIUrl":"10.33393/jcb.2026.3633","url":null,"abstract":"<p><strong>Introduction: </strong>Traumatic brain injury (TBI) is linked to poor progression and a high mortality rate. It is classified and evaluated using the standard Glasgow Coma Scale (GCS). In addition, serum biomarkers, such as vascular endothelial growth factor (VEGF), procalcitonin (PCT), and tumor necrosis factor-alpha (TNF-α), may facilitate accurate TBI severity evaluation, thereby assisting in its prognosis and clinical outcome.</p><p><strong>Methods: </strong>This study included 20 patients with TBI aged ≥18 years who were admitted within 12 h of injury to the intensive care unit (ICU). Serum samples for assessing VEGF, TNF-α, and PCT concentrations were acquired at admission 0 h, 24 h, and 72 h and analyzed by ELISA.</p><p><strong>Results: </strong>Serum concentrations of VEGF, TNF-α, and PCT (<i>p <</i> 0.0001) were significantly elevated at all time intervals in patients with TBI than in the control group (healthy individuals). Compared to the admission (0 h) time point, VEGF concentrations exhibited no significant differences among different time points, whereas TNF-α concentrations had increased significantly (<i>p <</i> 0.001<i>)</i> at 24 h. PCT concentrations exhibited a continuous elevation through time points, peaking at 72 h (<i>p <</i> 0.01)<i>.</i> The highest diagnostic performance for PCT was noted at 72 h, with an AUC of 0.834 (<i>p</i> < 0.004). In addition, PCT and VEGF showed a significant negative correlation at 24 h, indicating potential opposing roles in trauma response.</p><p><strong>Conclusion: </strong>Serum PCT concentrations can be utilized to track the progression of TBI because of a continuous increase in its concentration with time.</p>","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":"15 ","pages":"31-37"},"PeriodicalIF":0.0,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13192403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148017817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulatory biomarkers for microbial infections.","authors":"Vijay Kothari","doi":"10.33393/jcb.2026.3777","DOIUrl":"10.33393/jcb.2026.3777","url":null,"abstract":"<p><p>This article explores the paradigm shift in infectious disease diagnostics from direct pathogen detection to host-response profiling. While traditional markers like C-reactive protein (CRP) and procalcitonin (PCT) are clinical staples, they lack the specificity required for precision antimicrobial stewardship. The perspective highlights the emergence of presepsin as a superior early-phase bacterial biomarker and the development of multi-parametric mRNA signatures that differentiate viral from bacterial etiologies with high sensitivity. Furthermore, the expansion into pan-microbial surveillance, incorporating fungal (BDG, Galactomannan) and protozoal (HRP2/pLDH) markers, addresses critical blind spots in empiric therapy. Despite challenges regarding cost and standardization, the integration of these circulatory biomarkers with AI-driven decision support is poised to slowly replace empiric treatment with precision stewardship. This transition enables the triangulation of infection etiology within the clinical \"golden hour\", ultimately improving patient outcomes and combating antibiotic resistance.</p>","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":"15 ","pages":"28-30"},"PeriodicalIF":0.0,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13159466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147934164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysfunctional high-density lipoprotein predicts survival, renal recovery and the need for kidney replacement therapy in acute kidney injury.","authors":"Nikolaos Pagonas, Oliver Pfeifer, Stefan Erfurt, Meike Hoffmeister, Oliver Ritter, Theodoros Kelesidis, Daniel Patschan","doi":"10.33393/jcb.2026.3584","DOIUrl":"10.33393/jcb.2026.3584","url":null,"abstract":"<p><strong>Introduction: </strong>There is growing evidence that oxidative stress contributes not only to the pathophysiology of atherosclerosis but also to acute kidney injury (AKI). This study investigated the prognostic value of nHDL_ox (normalized high-density lipoprotein with reduced antioxidant function) in hospitalized patients with AKI.</p><p><strong>Methods: </strong>nHDL_ox was measured within 48 hours of AKI diagnosis. We assessed its performance in predicting the following primary endpoints: in-hospital all-cause mortality, need for kidney replacement therapy (KRT), and restoration of kidney function before discharge. Secondary endpoints included clinical markers of severe disease course: intensive care treatment, ventilatory support, and vasopressor requirement.</p><p><strong>Results: </strong>Among 132 participants, 16.7% died in the hospital, 36.4% required KRT, and 31.1% had no restoration of kidney function. For all primary endpoints, nHDL_ox levels were significantly higher in non-survivors (2.00 vs. 1.26; +58.7%; p = 0.009), in patients requiring KRT (1.66 vs. 1.23; +34.9%; p = 0.002), and in those without renal recovery (1.71 vs. 1.23; +39.0%; p = 0.001). nHDL_ox was independently associated with death, KRT, and lack of renal recovery, with odds ratios for a twofold increase (95% CI) of 1.88 (1.19-2.98), 1.78 (1.17-2.69), and 2.09 (1.34-3.26), respectively. Predictive performance was moderate, with AUC-ROC values (95% CI) of 0.68 (0.54-0.81), 0.66 (0.56-0.76), and 0.67 (0.57-0.78). No differences were observed across secondary endpoints.</p><p><strong>Conclusions: </strong>Impaired antioxidant HDL function is closely associated with clinically relevant AKI outcomes. nHDL_ox, therefore, represents a significant risk factor in both cardiovascular and kidney disease.</p>","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":"15 ","pages":"16-27"},"PeriodicalIF":0.0,"publicationDate":"2026-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12994525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147481098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum in: Association of hypertension and diabetes with COVID-19 severity in comparison to healthy patients.","authors":"Muslima Mahmood Ismail, Abdulhakeem D Hussein, Othman Ghazi Najeeb, Mohammed Hadi Ali Al-Jumaili","doi":"10.33393/jcb.2026.3769","DOIUrl":"10.33393/jcb.2026.3769","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.33393/jcb.2025.3561.].</p>","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":"15 ","pages":"15"},"PeriodicalIF":0.0,"publicationDate":"2026-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12965151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147379146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Secretory versus non-secretory hepatocellular carcinoma: associations of serum AFP, CEA and CA19-9 levels with clinical presentation, metastatic patterns, and survival.","authors":"Muhammad Emmamally, Urda Kotze, Rufaida Khan, Marc Bernon, Sanju Sobnach, Jake Ej Krige, C Wendy Spearman, Mark Sonderup, Eduard Jonas","doi":"10.33393/jcb.2026.3637","DOIUrl":"10.33393/jcb.2026.3637","url":null,"abstract":"<p><strong>Introduction: </strong>Hepatocellular carcinoma (HCC) is a global health challenge, with disproportionately high mortality rates in low- and middle-income countries (LMICs). Tumor markers such as alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9) are used for diagnostic purposes and for monitoring treatment results. The relationship between these markers, individually or in combination, with clinical presentation, metastatic patterns and survival outcomes has not been extensively researched.</p><p><strong>Methods: </strong>In this South African retrospective study, we assess the association of the tumor marker levels on presentation, diagnosis, and prognosis. Data was analyzed using chi-square tests, t-tests, and Kaplan-Meier survival analysis.</p><p><strong>Results: </strong>The study included 501 patients, treated between 2010 and 2024. Elevated AFP levels were associated with chronic hepatitis B virus (HBV) infection, hepatomegaly, and pulmonary metastases, while elevated CA19-9 levels were associated with more advanced liver disease. Survival analysis confirmed shorter survival for patients with elevated AFP and CA19-9 levels compared to normal levels (p < 0.001). Elevated CEA levels were not significantly associated with survival. Patients with no elevated markers (i.e., \"triple-negative\" for AFP, CEA, and CA19-9) had the longest survival, compared to those with multiple elevated markers (p < 0.001).</p><p><strong>Conclusion: </strong>AFP and CA19-9 elevations were associated with more advanced disease and poorer survival outcomes. We emphasize the importance of integrating tumor marker levels with imaging and histopathology for a multimodal diagnostic approach. Further research is needed to validate these associations to better define the role of biomarkers in HCC management.</p>","PeriodicalId":37524,"journal":{"name":"Journal of Circulating Biomarkers","volume":"15 ","pages":"8-14"},"PeriodicalIF":0.0,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12856566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146107814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}