Biomarkers For Early Diagnosis Research Articles

Autoantibodies as important biomarkers in early diagnosis of type-1 diabetes

Autoantibodies as important biomarkers in early diagnosis of type-1 diabetes

Urinary dipeptidase 1 and trefoil factor 1 are promising biomarkers for early diagnosis of colorectal cancer.

Currently utilized serum tumor markers and fecal immunochemical tests do not have sufficient diagnostic power for colorectal cancer (CRC) due to their low sensitivities. To establish non-invasive urinary protein biomarkers for early CRC diagnosis, we performed stepwise analyses employing urine samples from CRCs and healthy controls (HCs). Among 474 urine samples, 363 age- and sex-matched participants (188 HCs, 175 stage 0-III CRCs) were randomly divided into discovery (16 HCs, 16 CRCs), training (110 HCs, 110 CRCs), and validation (62 HCs, 49 CRCs) cohorts. Of the 23 urinary protein candidates comprehensively identified from mass spectrometry in the discovery cohort, urinary levels of dipeptidase 1 (uDPEP1) and Trefoil factor1 (uTFF1) were the two most significant diagnostic biomarkers for CRC in both training and validation cohorts using enzyme-linked immunosorbent assays. A urinary biomarker panel comprising uDPEP1 and uTFF1 significantly distinguished CRCs from HCs, showing area under the curves of 0.825-0.956 for stage 0-III CRC and 0.792-0.852 for stage 0/I CRC. uDPEP1 and uTFF1 also significantly distinguished colorectal adenoma (CRA) patients from HCs, with uDPEP1 and uTFF1 increasing significantly in the order of HCs, CRA patients, and CRC patients. Moreover, expression levels of DPEP1 and TFF1 were also significantly higher in the serum and tumor tissues of CRC, compared to HCs and normal tissues, respectively. This study established a promising and non-invasive urinary protein biomarker panel, which enables the early detection of CRC with high sensitivity.

Evaluating Biomarkers as Tools for Early Detection and Prognosis of Heart Failure: A Comprehensive Review.

There is a high prevalence of heart failure (HF) worldwide, which has significant consequences for healthcare costs, patient death and quality of life. Therefore, there has been much focus on finding and using biomarkers for early diagnosis, prognostication and therapy of HF. This overview of the research presents a thorough examination of the current state of HF biomarkers and their many uses. Their function in diagnosing HF, gauging its severity and monitoring its response to therapy are all discussed. Particularly promising in HF diagnosis and risk stratification are the cardiac-specific biomarkers, B-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide. Markers of oxidative stress, extracellular matrix, renal function, inflammation and cardiac peptides have shown promise in evaluating HF severity and prognosis. MicroRNAs and insulin-like growth factor are two emerging biomarkers that have shown potential in helping with HF diagnosis and prognosis.

Chemokine ligand 14 correlates with immune cell infiltration in the gastric cancer microenvironment in predicting unfavorable prognosis.

Gastric cancer (GC) is the world's third-leading cause of cancer-related mortality; the prognosis for GC patients remains poor in terms of a lack of reliable biomarkers for early diagnosis and immune therapy response prediction. Here, we aim to discover the connection between chemokine ligand 14 (CCL14) expression in the gastric tumor microenvironment (TME) and its clinical significance and investigate its correlation with immune cell infiltration. We assessed CCL14 mRNA expression and its interrelation with tumor-infiltrating immune cells (TILs) using bioinformatics analysis in gastric cancer. CCL14 protein expression, TILs, and immune checkpoints were detected by multiple immunohistochemistry analyses in gastric cancer tissue microarrays. Then, we conducted statistics analysis to determine the association between CCL14-related patient survival and immune cell infiltration (p < 0.05). We found that the CCL14 protein was separately expressed in the carcinoma cells and TILs in stomach cancer tissues. The CCL14 protein was related to tumor differentiation and tumor depth and positively correlated with the presentation of LAG3 and PD-L1 in gastric cancer cells. In addition, the CCL14 protein in the TILs of gastric cancer tissues was related to Lauren's type cells, T cells (CD4+ and CD8+), and CD68+ macrophages in the TME. Kaplan-Meier survival and multivariate analyses showed that the CCL14 expression in gastric cancer cells was an independent prognostic factor. Our study illustrated that CCL14 is a poor prognosis biomarker in gastric cancer, which may be associated with the potential for immunotherapy.

Analysis of Metabolic Changes in Endogenous Metabolites and Diagnostic Biomarkers for Various Diseases Using Liquid Chromatography and Mass Spectrometry.

Analysis of endogenous metabolites in various diseases is useful for searching diagnostic biomarkers and elucidating the molecular mechanisms of pathophysiology. The author and collaborators have developed some LC/tandem mass spectrometry (LC/MS/MS) methods for metabolites and applied them to disease-related samples. First, we identified urinary conjugated cholesterol metabolites and serum N-palmitoyl-O-phosphocholine serine as useful biomarkers for Niemann-Pick disease type C (NPC). For the purpose of intraoperative diagnosis of glioma patients, we developed the LC/MS/MS analysis methods for 2-hydroxyglutaric acid or cystine and found that they could be good differential biomarkers. For renal cell carcinoma, we searched for various biomarkers for early diagnosis, malignancy evaluation and recurrence prediction by global metabolome analysis and targeted LC/MS/MS analysis. In pathological analysis, we developed a simultaneous LC/MS/MS analysis method for 13 steroid hormones and applied it to NPC cells, we found 6 types of reductions in NPC model cells. For non-alcoholic steatohepatitis (NASH), model mice were prepared with special diet and plasma bile acids were measured, and as a result, hydrophilic bile acids were significantly increased. In addition, we developed an LC/MS/MS method for 17 sterols and analyzed liver cholesterol metabolites and found a decrease in phytosterols and cholesterol synthetic markers and an increase in non-enzymatic oxidative sterols in the pre-onset stage of NASH. We will continue to challenge themselves to add value to clinical practice based on cutting-edge analytical chemistry methodology.

Development of a serum miRNA panel for detection of early stage non-small cell lung cancer.

3058 Background: Lung cancer remains the leading cause of cancer deaths, largely due to late-stage diagnosis. Early detection significantly improves survival rates, but current methods like chest X-rays and low-dose CT (LDCT) scans face limitations in sensitivity and specificity. MicroRNAs (miRNAs) are small non-coding RNAs whose dysregulation has been widely observed in different stages of cancer. Evidence suggests that circulating miRNAs could be promising biomarkers for early diagnosis of lung cancer. In this study, we developed and validated a 15-miRNA panel as a blood-based minimally invasive test for early detection of non-small cell lung cancer (NSCLC) using the proprietary multiplex quantitative real-time PCR (qPCR). Methods: 332 serum samples (182 Stage I&amp;II NSCLC, 150 healthy controls) were divided into training (n=266) and validation (n=66) cohorts. Differentially expressed serum miRNAs were screened with Miseq sequencing followed by qPCR validation. The multi-miR panel was developed with a logistic regression model and validated using an independent cohort. Receiver operating characteristic curves were constructed to evaluate the diagnostic accuracy of the panel. A stem-loop quadruplex qPCR assay was invented for concurrent detection of 4 miRs in a single reaction. Results: 15 differentially expressed miRNAs were selected for logistic model construction based on their Ct values (Ct&lt;35) and high diagnostic accuracy of stage I&amp;II NSCLC (AUC&gt;0.7). The 15-miRNA panel model achieved 88.4% sensitivity, 81.7% specificity (AUC = 0.912) in the training cohort (Table), and was validated with 94.4% sensitivity, 73.3% specificity (AUC = 0.892) in the validation cohort. Quantification of 15 miRs and 1 internal control was performed in 4 reactions tubes via quadruplex qPCR assay. Conclusions: The serum 15-miR panel developed and validated in this retrospective study exhibited robust performance for detection of early stage NSCLC. The panel demonstrates potential diagnostic applications and clinical utility to be implemented together with LDCT in current lung cancer screening program as a blood biomarker to reduce false positive results. In addition, the proposed stem-loop quadruplex qPCR system offers an efficient and promising approach for miRNA profiling in future clinical applications. [Table: see text]

The role of ATP-binding cassette subfamily G member 1 in tumor progression.

ATP-binding cassette subfamily G member 1 is mostly known as a transporter for intracellular cholesterol efflux, and a number of studies indicate that ABCG1 also functions actively in tumor initiation and progression. This review aimed to provide an overall review of how ABCG1 acts in tumor progression. A comprehensive searching about ABCG1 and tumor was conducted up to November 2023 using proper keywords through databases including PubMed and Web of Science. Overall, ABCG1 plays a crucial role in the development of multiple tumorigenesis. ABCG1 enhances tumor-promoting ability through conferring stem-like properties to cancer cells and mediates chemoresistance in multiple cancers. Additionally, ABCG1 may act as a kinase to phosphorylate downstream molecules and induces tumor growth. In tumor microenvironment, ABCG1 plays a substantial role in immunity response through macrophages to create a tumor-favoring circumstance. High expression of ABCG1 is usually associated with poor prognosis, which means ABCG1 may be a potential biomarker for early diagnosis and prognosis of various cancers. ABCG1-targeted therapy may provide a novel treatment for cancer patients.

Unlocking the potential of the 3-hydroxykynurenine/kynurenic acid ratio: a promising biomarker in adolescent major depressive disorder.

Metabolites disruptions in tryptophan (TRP) and kynurenine pathway (KP) are believed to disturb neurotransmitter homeostasis and contribute to depressive symptoms. This study aims to investigate serum levels of KP metabolites in adolescent major depressive disorder (AMDD), and examine their relationship with depression severities. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to analyze serum levels of TRP, kynurenic acid (KYNA), kynurenine (KYN), and 3-hydroxy-kynurenine (3-HK) in 143 AMDD participants and 98 healthy controls (HC). Clinical data, including Children's Depression Inventory (CDI) scores, were collected and analyzed using statistical methods, such as ANOVA, logistic regression, Receiver operating characteristic curve analysis and a significance level of p < 0.05 was used for all analyses. AMDD showed significantly decreased serum levels of KYNA (-25.5%), KYN (-14.2%), TRP (-11.0%) and the KYNA/KYN ratio (-11.9%) compared to HC (p < 0.01). Conversely, significant increases were observed in 3-HK levels (+50.4%), the 3-HK/KYNA ratio (+104.3%) and the 3-HK/KYN ratio (+93.0%) (p < 0.01). Logistic regression analysis identified increased level of 3-HK as a contributing factor to AMDD, while increased level of KYNA acted as a protective factor against AMDD. The 3-HK/KYNA ratio demonstrated an area under the curve (AUC) of 0.952. This study didn't explore AMDD's inflammatory status and its metabolites relationship explicitly. These findings indicate that metabolites of TRP and KP may play a crucial role in the pathogenesis of AMDD, emphasizing the potential of the 3-HK/KYNA ratio as a laboratory biomarker for early detection and diagnosis of AMDD.

Cascade CRISPR/Cas12a and DSN for the electrochemical biosensing of miR-1246 in BC-derived exosomes

MiR-1246 in breast cancer-derived exosomes was a promising biomarker for early diagnosis of breast cancer(BC). However, the low abundance, high homology and complex background interference make the accurate quantitative detection of miR-1246 facing great challenges. In this study, we developed an electrochemical biosensor based on the subtly combined of CRISPR/Cas12a, double-stranded specific nuclease(DSN) and magnetic nanoparticles(MNPs) for the detection of miR-1246 in BC-derived exosomes. Ascribed to the good synergistic effect of DSN, Cas12a and MNPs, the developed electrochemical biosensor exhibited excellent performance with the linear range from 500 aM to 5 pM, and the detection limit as low down to about 50 aM. The target-specific triggered enzyme-digest activity of DSN and Cas12a system, as well as the powerful separation ability of MNPs ensure the high specificity of developed electrochemical biosensor which can distinguish single base mismatches. In addition, the developed electrochemical biosensor has been successfully applied to detect miR-1246 in blood-derived exosomes and realize distinguishing the BC patients from the healthy individuals. It is expected that the well-designed biosensing platform will open up new avenues for clinical liquid biopsy and early screening of breast cancer, as well as provide deeper insights into clinical oncology treatment.

Heterogeneous Analysis of Extracellular Vesicles for Osteosarcoma Diagnosis.

Osteosarcoma (OS) is the most prevalent primary tumor of bones, often diagnosed late with a poor prognosis. Currently, few effective biomarkers or diagnostic methods have been developed for early OS detection with high confidence, especially for metastatic OS. Tumor-derived extracellular vesicles (EVs) are emerging as promising biomarkers for early cancer diagnosis through liquid biopsy. Here, we report a plasmonic imaging-based biosensing technique, termed subpopulation protein analysis by single EV counting (SPASEC), for size-dependent EV subpopulation analysis. In our SPASEC platform, EVs are accurately sized and counted on plasmonic sensor chips coated with OS-specific antibodies. Subsequently, EVs are categorized into distinct subpopulations based on their sizes, and the membrane proteins of each size-dependent subpopulation are profiled. We measured the heterogeneous expression levels of the EV markers (CD63, BMP2, GD2, and N-cadherin) in each of the EV subsets from both OS cell lines and clinical plasma samples. Using the linear discriminant analysis (LDA) model, the combination of four markers is applied to classify the healthy donors (n = 37), nonmetastatic OS patients (n = 13), and metastatic patients (n = 12) with an area under the curve of 0.95, 0.92, and 0.99, respectively. SPASEC provides accurate EV sensing technology for early OS diagnosis.

Identification of the biological functions and chemo-therapeutic responses of ITGB superfamily in ovarian cancer

BackgroundPatients with ovarian cancer (OC) tend to face a poor prognosis due to a lack of typical symptoms and a high rate of recurrence and chemo-resistance. Therefore, identifying representative and reliable biomarkers for early diagnosis and prediction of chemo-therapeutic responses is vital for improving the prognosis of OC.MethodsExpression levels, IHC staining, and subcellular distribution of eight ITGBs were analyzed using The Cancer Genome Atlas (TCGA)-Ovarian Serous Cystadenocarcinoma (OV) database, GEO DataSets, and the HPA website. PrognoScan and Univariate Cox were used for prognostic analysis. TIDE database, TIMER database, and GSCA database were used to analyze the correlation between immune functions and ITGBs. Consensus clustering analysis was performed to subtype OC patients in the TCGA database. LASSO regression was used to construct the predictive model. The Cytoscape software was used for identifying hub genes. The ‘pRRophetic’ R package was applied to predict chemo-therapeutic responses of ITGBs.ResultsITGBs were upregulated in OC tissues except ITGB1 and ITGB3. High expression of ITGBs correlated with an unfavorable prognosis of OC except ITGB2. In OC, there was a strong correlation between immune responses and ITGB2, 6, and 7. In addition, the expression matrix of eight ITGBs divided the TCGA-OV database into two subgroups. Subgroup A showed upregulation of eight ITGBs. The predictive model distinguishes OC patients from favorable prognosis to poor prognosis. Chemo-therapeutic responses showed that ITGBs were able to predict responses of common chemo-therapeutic drugs for patients with OC.ConclusionsThis article provides evidence for predicting prognosis, immuno-, and chemo-therapeutic responses of ITGBs in OC and reveals related biological functions of ITGBs in OC.

Lipidomic analysis of serum exosomes identifies a novel diagnostic marker for type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) intricately involves disrupted lipid metabolism. Exosomes emerge as carriers of biomarkers for early diagnosis and monitoring. This study aims to identify lipid metabolites in serum exosomes for T2DM diagnosis. Serum samples were collected from newly diagnosed T2DM patients and age and body mass index-matched healthy controls. Exosomes were isolated using exosome isolation reagent, and untargeted/targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to identify and validate altered lipid metabolites. Receiver operating characteristic curve analysis was used to evaluate the diagnostic value of candidate lipid metabolites. Serum exosomes were successfully isolated from both groups, with untargeted LC-MS/MS revealing distinct lipid metabolite alterations. Notably, phosphatidylethanolamine (PE) (22:2(13Z,16Z)/14:0) showed stable elevation in T2DM-serum exosomes. Targeted LC-MS/MS confirmed significant increase of PE (22:2(13Z,16Z)/14:0) in T2DM exosomes but not in serum. PE (22:2(13Z,16Z)/14:0) levels not only positively correlated with hemoglobin A1C levels and blood glucose levels, but also effectively distinguished T2DM patients from healthy individuals (area under the curve = 0.9141). Our research sheds light on the importance of serum exosome lipid metabolites in diagnosing T2DM, providing valuable insights into the complex lipid metabolism of diabetes.

The diagnostic potential role of thioredoxin reductase and TXNRD1 in early lung adenocarcinoma: A cohort study

BackgroundLung adenocarcinoma (LUAD) is the primary form of lung cancer, yet the reliable biomarkers for early diagnosis remain insufficient. Thioredoxin reductase (TrxR) is strongly linked to the occurrence, development, and drug resistance of lung cancer, making it a potential biomarker. However, further research is required to assess its diagnostic value in LUAD. MethodsA retrospective analysis was performed on patients who underwent pulmonary nodule resection at our center from 2018 to 2022. Clinical data, including preoperative TrxR levels, imaging, and laboratory characteristics, were identified as study variables. Two prediction models were constructed using multiple logistic regression, and their prediction performance was evaluated comprehensively. Besides, bioinformatics analyses of TrxR coding genes including differential expression, functional enrichment, immune infiltration, drug sensitivity, and single-cell landscape were performed based on TCGA database, which were subsequently validated by Human Protein Atlas. ResultsA total of 506 eligible patients (72 benign lesions, 77 AISs, 185 MIAs and 172 IACs) were identified in the clinical cohort. Two TrxR-based models were developed, which were able to distinguish between benign and malignant pulmonary nodules, as well as pathological subtypes of LUAD, respectively. The models exhibited good predictive ability with all AUC values ranging from 0.7 to 0.9. Based on calibration curves and clinical decision analysis, the nomogram models showed high reliability. Functional analysis indicated that TXNRD1 primarily participated in cell cycle and lipid metabolism. Immune infiltration analysis showed that TXNRD1 has a strong association with immune cells and could impact immunotherapy. Then, we identified small molecular compounds that inhibit TXNRD1 and confirmed TXNRD1 expression by single-cell landscape and immunohistochemistry. ConclusionThis study validated the diagnostic value of TrxR and TXNRD1 in clinical cohorts and transcriptional data, respectively. TrxR and TXNRD1 could be used in the risk diagnosis of early LUAD and facilitate personalized treatment strategies.

Unmet needs in axial spondyloarthritis. Proceedings of the French spondyloarthritis taskforce workshop

The progress observed over the last 30 years in the field of axial spondyloarthritis (axSpA) has not made it possible to answer all the current questions. This manuscript represents the proceedings of the meeting of the French spondyloArthitiS Task force (FAST) in Besançon on September 28 and 29, 2023. Different points of discussion were thus individualized as unmet needs: biomarkers for early diagnosis and disease activity, a common electronic file dedicated to SpA nationwide, a better comprehension of dysbiosis in the disease, a check-list for addressing to the rheumatologist, adapt patient reported outcomes thresholds for female gender, implementation of comorbidities screening programs, new imaging tools, in research cellular and multi omics approaches, grouping, at a nationwide level, different cohorts and registries, therapeutic strategy studies, consensual definition of difficult to treat disease and management, preclinical stage of the disease, mastering AI as a tool in the various aspects of research. These elements may represent a framework for the research agenda in axSpA for the years to come.

Isocitrate dehydrogenase 1 upregulation in urinary extracellular vesicles from proximal tubules of type 2 diabetic rats.

Diabetic nephropathy (DN) is a major cause of chronic kidney disease. Microalbuminuria is currently the most common non-invasive biomarker for the early diagnosis of DN. However, renal structural damage may have advanced when albuminuria is detected. In this study, we sought biomarkers for early DN diagnosis through proteomic analysis of urinary extracellular vesicles (uEVs) from type 2 diabetic model rats and normal controls. Isocitrate dehydrogenase 1 (IDH1) was significantly increased in uEVs from diabetic model rats at the early stage despite minimal differences in albuminuria between the groups. Calorie restriction significantly suppressed the increase in IDH1 in uEVs and 24-hour urinary albumin excretion, suggesting that the increase in IDH1 in uEVs was associated with the progression of DN. Additionally, we investigated the origin of IDH1-containing uEVs based on their surface sugar chains. Lectin affinity enrichment and immunohistochemical staining showed that IDH1-containing uEVs were derived from proximal tubules. These findings suggest that the increase in IDH1 in uEVs reflects pathophysiological alterations in the proximal tubules and that IDH1 in uEVs may serve as a potential biomarker of DN in the proximal tubules.

#1669 Gangliosides as biomarkers for early diagnosis of diabetic kidney disease: detection and characterization by high-performance mass spectrometry

Abstract Background and Aims The early identification of diabetic kidney disease (DKD) is crucial as it may facilitate immediate intervention, thus impeding the progression of the condition and the risk of developing end-stage renal disease (ESRD). Enhancing our understanding of the pathophysiology of this microvascular complication as well as developing therapeutic strategies are imperative. Hence, the aim of the current study was to address the problematics of detection and characterization of gangliosides in the urine of type 2 diabetes mellitus (DM) patients with DKD. Method In this cross-sectional study, the urine ganglioside content from 24 h collected urine samples of 60 type 2 DM patients (20 with normal to mildly increased albuminuria—A1 group, 20 with moderately increased albuminuria—A2 group, 20 with severe increased albuminuria—A3 group) was compared to that of 20 healthy controls using a promising technique based on high-resolution (HR) mass spectrometry (MS). Furthermore, for structural elucidation of individual compounds, we isolated the ions GT1 (d18:1/18:0), identified at m/z 708.3379 and, GQ1 (d18:1/18:0) at m/z 812.7068, observed only in the screening analysis of A3 patients, and exposed them to Higher-energy collisional dissociation (HCD MS/MS) in the negative ion mode. Results Patients with type 2 diabetes mellitus display a considerably greater abundance of different species in their urinary gangliosidome, which varies in either glycan or ceramide structure, in comparison to the control group. Even within the A1 group, a greater variety of structures exhibiting varying degrees of sialylation were observed. A wide range of carbohydrate chains were discovered, ranging from short, monosialylated chains (GM) to complex, pentasialylated chains (GP). Additionally, some ganglioside chains were modified with and O-acetyl (O-Ac) attachments. The gangliosidome of the A3 group comprises a higher variety of structures, compared to A1 and A2, differing in their overall sialic acid content, and more complex structures, including various biologically significant modifications, such as O-fucosylation, O-GalNAc and CH3COO− attachments. Both albuminuria and glomerular filtration rate proved to be correlated with the degree of sialylation of species. Furthermore, significant alterations occur also in the ceramide part, with the most noteworthy being the presence of sphingoid base trihydroxylation, which is shown in both A1 and A3 samples. Additionally, A3 exhibits unusual length of the fatty acid chains. GQ1d(d18:1/18:0), GT1α(d18:1/18:0), and GT1b(d18:1/18:0) were identified as predictive for specific isomers linked to the location of Neu5Ac along the oligosaccharide structure using HCD-based MS/MS. Conclusion We concluded that gangliosides may be involved in the development and progression of DKD through the use of mass spectrometry techniques, which provides considerable precision and ultrahigh reproducibility, sensitivity and processing power, and the capability to identify minor elements in complex biological matrices. Thus, a set of promising bioindicators for early detection and progression of DKD was established. Even in the normoalbuminuric stage, the sialylation level of the expressed species appears to be an extremely important biochemical marker of DKD. Moreover, the modifications detected in the composition of ceramide indicate that, alongside the oligosaccharide structure, the lipid component might function as a specific molecular indicator for different stages of DKD. The presence of a few isomers in the A3 group has been discovered to be associated with DKD progression, based on the informative sequence ions obtained from the structural analysis. Moreover, gangliosides might be used as target molecules for the implementation of therapeutic schemes in type 2 DM patients.

Autoantibodies against Endophilin A2 as a novel biomarker are beneficial to early diagnosis of breast cancer

BackgroundDue to the lack of early symptoms, breast cancer is frequently overlooked, leading to distant metastases and multi-organ lesions that directly threaten patients’ lives. We have identified a novel tumor marker, antibodies to endophilin A2 (EA2), to improve early diagnosis of breast cancer. MethodsAntibody levels of EA2 were analyzed in sera of patients with cancers of different origins and stages by indirect enzyme-linked immunosorbent assay (ELISA). Diagnostic accuracy and reference range were determined by the area under the receiver operating curve and distribution curve. The levels of EA2 antigen in sera were determined by sandwich ELISA. ResultsThe levels of antibodies against EA2 were higher in sera of patients with breast cancer (P < 0.0001), liver cancer (P = 0.0005), gastric cancer (P = 0.0026), and colon cancer (P = 0.0349) than those in healthy controls, but not in patients with rectal cancer (P = 0.1151), leukemia (P = 0.7508), or lung cancer (P = 0.2247). The highest diagnostic value was for breast cancer, particularly in early cases (AUC = 0.8014) and those with distant metastases (AUC = 0.7885). The titers of EA2 antibodies in sera were correlated with levels of EA2 antigen in breast cancer patients. ConclusionAntibodies to EA2 are novel blood biomarkers for early diagnosis of breast cancer that warrants further study in larger-scale cohort studies.

#3050 Hemodynamic study of hypertensive disorders in pregnancy using cardiothoracic bioimpedance

Abstract Background and Aims Hypertensive disorders in pregnancy (HDP) are a major cause of maternal and perinatal morbidity and mortality. There is still a need for the development of biomarkers for early diagnosis of the severity of the condition. Thoracic electrical bioimpedance (TEB) is a non-invasive hemodynamic technique based on the resistance to the flow of electrical current. We investigated hemodynamic changes in pregnant/postpartum women with HDP using TEB. Method A retrospective observational study was conducted in pregnant and postpartum women with hypertension monitored by TEB. Indirect changes were analyzed in: cardiac work, left cardiac work index (LCWI kg⋅m/m2) and calculated cardiac output (CO ml/min=systolic volume -SV ml- × heart rate -HR bpm-); fluid status, thoracic fluid content index (TFCI l/kOhm/m2); and resistances, systemic vascular resistance index (SVRI dyn.s.cm-5.m2). Normality of variables was assessed by Shapiro-Wilk test and correlation analysis was performed by Pearson/Spearman tests. Statistical inference between the hypertension-preeclampsia and pregnancy-postpartum groups was performed using Student's/Mann-Whitney U tests. Analysis was performed using STATA 12. Results Fifty-five patients were included with a mean age of 36.5 years (SD 4.54), 69% were older than 35 years. Pregnant women accounted for 86% of the TEB evaluations, the majority (93.6%) in the third trimester. There was chronic hypertension in 7.27% and pre-eclampsia in 18.18% of previous pregnancies. The diagnoses were: pre-eclampsia (56.36%), gestational hypertension (40%) and HELLP syndrome (3.64%). The mean blood pressure was 144/89 (SD 16/11) mmHg. Mean proteinuria was 363.2 (range: 10.3-23220) mg/g. The median values were as follow: LCWI: 5.05 (IQR: 1.4) kg⋅m/m2; CO: 6352 (IQR: 2345) ml/min; TFCI: 17.9 (IQR: 6.3) l/kOhm/m2; SVRI: 2167.63 (SD: 462.87) dyn.s.cm-5.m2. LCWI showed a weak positive correlation with systolic blood pressure (SBP) and a strong correlation with diastolic blood pressure (DBP) (Rho 0.2899 and 0.5176, respectively). There was also a positive and moderate correlation between SVRI and SBP and DBP (r 0.4265 and 0.4019, respectively). There was no correlation between CO or TFCI and SBP or DBP. No statistically significant differences in hemodynamic parameters were found between gestational hypertension and pre-eclampsia, nor between pregnant and postpartum women. Conclusion Increased blood pressure in the setting of HDP correlates with increased LCWI and systemic resistance independent of fluid retention. An increase in systemic vascular resistance measured by TEB (which decreases in normal pregnancy) may be an early diagnostic marker of HDP. These findings require further validation in a larger cohort, including a control group of pregnant women without hypertension.

Multiarmed DNA jumper and metal-organic frameworks–functionalized paper-based bioplatform for small extracellular vesicle–derived miRNAs assay

Small extracellular vesicle–derived microRNAs (sEV-miRNAs) have emerged as promising noninvasive biomarkers for early cancer diagnosis. Herein, we developed a molecular probe based on three-dimensional (3D) multiarmed DNA tetrahedral jumpers (mDNA-Js)-assisted DNAzyme activated by Na+, combined with a disposable paper-based electrode modified with a Zr-MOF–rGO–Au NP nanocomplex (ZrGA) to fabricate a novel biosensor for sEV-miRNAs Assay. Zr-MOF tightly wrapped by rGO was prepared via a one-step method, and it effectively aids electron transfer and maximizes the effective reaction area. In addition, the mechanically rigid, and nanoscale-addressable mDNA-Js assembled from the bottom up ensure the distance and orientation between fixed biological probes as well as avoid probe entanglement, considerably improving the efficiency of molecular hybridization. The fabricated bioplatform achieved the sensitive detection of sEV-miR-21 with a detection limit of 34.6 aM and a dynamic range from100 aM to 0.2 µM. In clinical blood sample tests, the proposed bioplatform showed results highly consistent with those of qRT-PCRs and the signal increased proportionally with the NSCLC staging. The proposed biosensor with a portable wireless USB-type analyzer is promising for the fast, easy, low-cost, and highly sensitive detection of various nucleic acids and their mutation derivatives, making it ideal for POC biosensing.

Evaluation of diagnostic accuracy of urine neutrophil gelatinase-associated lipocalin in patients with symptoms of urinary tract infections: a meta-analysis.

Early and accurate diagnosis of urinary tract infection (UTI) can prevent serious sequelae including chronic kidney disease. Multiple individual studies have identified urine neutrophil gelatinase-associated lipocalin (uNGAL) as a promising biomarker for early diagnosis of UTI. We sought to understand the distribution and diagnostic accuracy of uNGAL values in patients presenting with UTI symptoms. Our systematic literature reviews in PubMed, Embase, and Cochrane Reviews up to March 2024, identified 25 studies reporting mean/median, standard deviation/quartiles, and detection limits of uNGAL in symptomatic patients with and without culture-confirmed UTI. Seventeen studies were in children. Meta-analyses were performed using the quantile estimation (QE) method estimating the distributions of uNGAL, which were then compared between the UTI and non-UTI groups for identifying the best cut-off points maximizing the Youden index. Sensitivity analyses were performed on all 25 studies including adult patients. We found that uNGAL levels were significantly higher in samples with confirmed UTI compared to those without. In pediatric studies, median and 95% confidence interval (CI) of uNGAL values were 22.41 (95% CI of 9.94, 50.54) ng/mL in non-UTI group vs. 118.85 (95% CI of 43.07, 327.97) ng/mL in UTI group. We estimated the cut-off point of 48.43 ng/mL with highest sensitivity (96%) and specificity (97%) in children. Sensitivity analysis including both pediatric and adult studies yielded similar results. The level of uNGAL in symptomatic patients with confirmed UTI is much higher than that reported in patients without UTI. It may be used as a diagnostic tool to identify UTI early among symptomatic patients. The range of uNGAL concentrations and cut-off points reported in subjects with UTI is much lower than that reported in patients with acute intrinsic kidney injury. https://www.crd.york.ac.uk/, PROSPERO (CRD42023370451).