Angiopoietin 2 as a Novel Potential Biomarker for Acute Aortic Dissection

Biomarker-assisted diagnosis of acute aortic dissection (AAD) is important for initiation of treatment and improved survival. However, identification of biomarkers for AAD in blood is a challenging task. The present study aims to find the potential AAD biomarkers using a transcriptomic strategy. Arrays based genome-wide gene expression profiling were performed using ascending aortic tissues which were collected from AAD patients and healthy donors. The differentially expressed genes were validated using quantitative reverse transcriptase PCR (qRT-PCR) and western blot. The plasma levels of a potential biomarker, angiopoietin 2 (ANGPT2) were determined in case-control cohort (77 AAD patients and 82 healthy controls) by enzyme linked immunosorbent assay. Receiver operating characteristic curve (ROC) was used to evaluate the diagnostic power of ANGPT2 for AAD. Transcriptome data demonstrated that a total of 18 genes were significantly up-regulated and 28 genes were significantly down-regulated among AAD tissues (foldchange>3.0, p < 0.01). By bioinformatic analysis, we identified ANGPT2 as a candidate biomarker for blood-based detection of AAD. The qRT-PCR and protein expression demonstrated that ANGPT2 increased 2.4- and 4.2 folds, respectively in aortic tissue of AAD patients. Immunohistochemical staining demonstrated that ANGPT2 was markedly increased in intima of the aortic wall in AAD. Furthermore, ANGPT2 was significantly elevated in AAD patients as compared with controls (median 1625 vs. 383 pg/ml, p < 1E-6). ROC curve analysis showed that ANGPT2 was highly predictive of a diagnosis of type A AAD (area under curve 0.93, p < 1E-6). Sensitivity and specificity were 81 and 90%, respectively at the cutoff value of 833 pg/ml. In conclusion, ANGPT2 could be a promising biomarker for diagnosis of AAD; however, more studies are still needed to verify its specificity in diagnosing of AAD.

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Serum amyloid a protein as a potential biomarker in predicting acute onset and association with in-hospital death in acute aortic dissection

BMC Cardiovascular Disorders ◽

10.1186/s12872-019-1267-0 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 1

Author(s):

Yuchen He ◽

Changcheng Ma ◽

Jia Xing ◽

Shiyue Wang ◽

Chao Ji ◽

...

Keyword(s):

Aortic Dissection ◽

Hospital Mortality ◽

Serum Amyloid A ◽

Acute Aortic Dissection ◽

Serum Amyloid ◽

Hospital Death ◽

Enzyme Linked Immunosorbent Assay ◽

Amyloid A ◽

Potential Biomarker ◽

Serum Amyloid A Protein

Abstract Background Acute aortic dissection (AAD) is a life-threatening disorder in vascular surgery with a high early mortality. Serum amyloid A (SAA) is a kind of acute-phase protein with a rapid diagnostic value in other diseases. However, the researches on the performance of SAA for the diagnosis of AAD is still lacking. This retrospective study aimed to evaluate the SAA levels and further explore its potential diagnostic role in AAD patients. Methods SAA levels were measured by enzyme-linked immunosorbent assay (ELISA) in 63 controls and 87 AAD patients. Laboratory examinations were also performed. And relative clinical information was collected from participants included in this study. Results SAA levels were significantly higher in AAD patients than those in healthy controls. SAA levels were independently associated with the risk of AAD. There was a positive significant correlation between SAA and C reactive protein (R = 0.442, and P = 0.001). Based on receiver-operating characteristic (ROC) analysis, the area under the curve (AUC) of SAA for the diagnosis of AAD were 0.942 with optimal cut-off points of 0.427 mg/L. For in-hospital mortality, the AUC of SAA were 0.732 with optimal cut-off points of 0.500 mg/L. According to logistic regression analysis, higher SAA levels represent a higher risk of in-hospital mortality (OR = 1.25; 95%CI: 1.07–1.47; P = 0.005). Conclusion Our findings demonstrated that SAA levels were significantly enhanced in AAD. SAA was closely correlated with inflammatory parameters and coagulation-related parameters in AAD. Furthermore, SAA could be a potential bio-marker for identifying AAD in the early diagnosis. Finally, SAA > 5.0 mg/L are independently related to AAD in-hospital mortality.

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S100A1 as a potential biomarker for the diagnosis of patients with acute aortic dissection

Journal of International Medical Research ◽

10.1177/03000605211004512 ◽

2021 ◽

Vol 49 (4) ◽

pp. 030006052110045

Author(s):

Chenjun Han ◽

Qiang Liu ◽

Yuanmin Li ◽

Wangfu Zang ◽

Jian Zhou

Keyword(s):

Logistic Regression ◽

Aortic Dissection ◽

Roc Curve ◽

Acute Aortic Dissection ◽

Troponin T ◽

Area Under The Curve ◽

Hospital Death ◽

Clinical Value ◽

Roc Curve Analysis ◽

Potential Biomarker

Objective Acute aortic dissection (AAD) is a common life-threatening cardiovascular disease. This retrospective study was conducted to analyze the plasma concentration of S100A1 and its diagnostic value for AAD through receiver operating characteristic (ROC) curve and logistic regression analyses. Methods Seventy-eight patients with AAD and 77 healthy controls were included, and the relevant clinical data for each group were collected. According to the Stanford classification, the AAD patients were divided into types A and B. The plasma levels of S100A1, D-dimer, hypersensitive C-reactive protein, and cardiac troponin T were detected by enzyme-linked immunosorbent assays. Results The S100A1 concentrations in the healthy control, Stanford A, and Stanford B groups were 0.7 ± 0.6, 4.9 ± 2.6, and 3.5 ± 2.2 ng/mL, respectively. The concentration of S100A1 was increased in patients with AAD complicated with aortic regurgitation, pericardial effusion, or in-hospital death. ROC curve analysis showed that the area under the curve was 0.89. Logistic regression analysis revealed that the S100A1 level was an important risk factor for the development of AAD. Conclusion Plasma S100A1 is significantly elevated in patients with AAD, and its concentration has potential clinical value for diagnosing AAD.

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Aggrecan: a new biomarker for acute type A aortic dissection

Scientific Reports ◽

10.1038/s41598-021-89653-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Karl C. König ◽

Harald Lahm ◽

Martina Dreßen ◽

Stefanie A. Doppler ◽

Stefan Eichhorn ◽

...

Keyword(s):

Aortic Dissection ◽

Troponin T ◽

Type A ◽

Aortic Aneurysms ◽

Aortic Tissue ◽

Acute Type ◽

Type A Aortic Dissection ◽

Potential Biomarker ◽

Aortic Pathology ◽

Creatine Kinase Mb

AbstractAcute type A aortic dissection (ATAAD) constitutes a life-threatening aortic pathology with significant morbidity and mortality. Without surgical intervention the usual mortality rate averages between 1 and 2% per hour. Thus, an early diagnosis of ATAAD is of pivotal importance to direct the affected patients to the appropriate treatment. Preceding tests to find an appropriate biomarker showed among others an increased aggrecan (ACAN) mRNA expression in aortic tissue of ATAAD patients. As a consequence, we investigated whether ACAN is a potential biomarker for diagnosing ATAAD. Mean ACAN protein concentration showed a significantly higher plasma concentration in ATAAD patients (38.59 ng/mL, n = 33) compared to plasma of patients with thoracic aortic aneurysms (4.45 ng/mL, n = 13), patients with myocardial infarction (11.77 ng/mL, n = 18) and healthy volunteers (8.05 ng/mL, n = 12). Cardiac enzymes like creatine kinase MB and cardiac troponin T showed no correlation with ACAN levels in ATAAD patients. Receiver-operator characteristics (ROC) curve analysis for ATAAD patients versus control subjects an optimum discrimination limit of ACAN plasma levels at 14.3 ng/mL with a corresponding sensitivity of 97% and specificity of 81%. According to our findings ACAN is a reliable potential biomarker in plasma samples to detect ATAAD with high sensitivity and specificity.

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Association among B lymphocyte subset and rheumatoid arthritis in a Chinese population

Journal of Orthopaedic Surgery and Research ◽

10.1186/s13018-021-02883-8 ◽

2021 ◽

Vol 16 (1) ◽

Author(s):

Haiyan You ◽

Mengwei Cheng ◽

Cui Ma ◽

Wenjuan Zheng ◽

Yu Jiang ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Healthy Subjects ◽

B Lymphocyte ◽

Lymphocyte Subsets ◽

Characteristic Curve ◽

Area Under The Curve ◽

Enzyme Linked Immunosorbent Assay ◽

Roc Curve Analysis ◽

Autoantibody Production ◽

Plasma Cytokines

Abstract Background and aim Autoantibody production are the main risk factors for inflammation of rheumatoid arthritis (RA). This study aimed to investigate differences in B lymphocyte subsets (native B, memory B, and plasmablasts) and several cytokines in RA patients and their correlation with the clinical parameters. Methods In total, 81 RA patients (active RA and inactive RA) and 40 healthy subjects were recruited between September 2018 and October 2020. The distribution of B lymphocyte subsets in peripheral blood samples was measured via flow cytometry and the plasma cytokines were detected by enzyme linked immunosorbent assay. The receiver operating characteristic curve (ROC) was used to evaluate the value of each index for RA diagnosis and activity prediction. Results The percentages of native B and memory B cells in RA patients did not differ significantly from the percentages of those in healthy controls. However, the percentage of plasmablasts in active RA patients was significantly higher compared with healthy subjects and inactive RA patients. The percentage of plasmablasts was significantly related to C reaction protein. ROC curve analysis showed that when the best cutoff value of plasmablasts/B cell was 1.08%, the area under the curve (AUC) for diagnosing RA was 0.831 (95% CI 0.748 ~ 0.915), the specificity was 91.4%, and the sensitivity was 67.5%. The AUC predicted by the combination of plasmablast and anti-CCP for active RA patients was 0.760, which was higher than that of plasmablast and anti-CCP. Conclusion In conclusion, the percentage of plasmablast varies among RA patients in different stages. The percentage of plasmablasts can be used as an early diagnosis marker for RA.

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Circulating microRNAs: a novel potential biomarker for diagnosing acute aortic dissection

Scientific Reports ◽

10.1038/s41598-017-13104-w ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 11

Author(s):

Jian Dong ◽

Junmin Bao ◽

Rui Feng ◽

Zhiqing Zhao ◽

Qingsheng Lu ◽

...

Keyword(s):

Aortic Dissection ◽

Acute Aortic Dissection ◽

Circulating Micrornas ◽

Potential Biomarker

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CXCL-8 in Preoperative Colorectal Cancer Patients: Significance for Diagnosis and Cancer Progression

International Journal of Molecular Sciences ◽

10.3390/ijms21062040 ◽

2020 ◽

Vol 21 (6) ◽

pp. 2040 ◽

Cited By ~ 1

Author(s):

Sara Pączek ◽

Marta Łukaszewicz-Zając ◽

Mariusz Gryko ◽

Piotr Mroczko ◽

Agnieszka Kulczyńska-Przybik ◽

...

Keyword(s):

Colorectal Cancer ◽

Tumor Marker ◽

Cancer Progression ◽

Characteristic Curve ◽

Distant Metastases ◽

Serum Levels ◽

Enzyme Linked Immunosorbent Assay ◽

Predictive Values ◽

Potential Biomarker ◽

Tumor Stages

Introduction. Since colorectal cancer (CRC) is the second most commonly diagnosed malignancy in Europe and third worldwide, novel biomarkers for diagnosing the disease are critically needed. Objectives. According to our knowledge, the present study is the first to evaluate the clinical usefulness of serum CXCL-8 (C-X-C motif chemokine 8) in the diagnosis and progression of CRC compared to classical tumor marker CEA (carcinoembryonic antigen) and marker of inflammation CRP (C-reactive protein). Patients and Methods. The study included 59 CRC patients and 46 healthy volunteers. Serum levels of selected proteins were measured using ELISA (enzyme-linked immunosorbent assay), CMIA (chemiluminescent microparticle immunoassay), and immunoturbidimetric methods. Results. Serum concentrations of CXCL-8, similarly to those of the classical tumor marker CEA and inflammatory state marker CRP, were significantly higher in CRC patients than in healthy controls. There were statistically significant differences in CXCL-8 concentrations between tumor stages, as established by the Kruskal–Wallis test and confirmed by the post hoc Dwass–Steele–Critchlow–Fligner test. CXCL-8 levels were also significantly elevated in CRC patients with distant metastases compared to patients in the subgroup without metastases. Diagnostic sensitivity, predictive values for negative results (NPV), and AUC (area under the Receiver Operating Characteristic Curve—ROC curve) of CXCL-8 were higher than those of CEA, while diagnostic specificity and predictive values for positive results (PPV) of CXCL-8 were higher than those of CRP. Conclusions. Our findings indicate greater utility of CXCL-8 in comparison to the classical tumor marker CEA in the diagnosis of CRC. Moreover, serum CXCL-8 might be a potential biomarker of colorectal cancer progression.

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Pathway Analysis of Differentially Expressed Genes in Patients with Acute Aortic Dissection

Biomarker Insights ◽

10.4137/bmi.s2530 ◽

2009 ◽

Vol 4 ◽

pp. BMI.S2530 ◽

Cited By ~ 19

Author(s):

Salah A. Mohamed ◽

Hans H. Sievers ◽

Thorsten Hanke ◽

Doreen Richardt ◽

Claudia Schmidtke ◽

...

Keyword(s):

Aortic Dissection ◽

Differentially Expressed Genes ◽

Pathway Analysis ◽

Acute Aortic Dissection ◽

Differentially Expressed ◽

Control Group ◽

Pathophysiological Mechanism ◽

Qrt Pcr ◽

Starting Point ◽

Fibrillin 1

Background Acute aortic dissection (AAD) is a life-threatening condition with high mortality and a relatively unclarified pathophysiological mechanism. Although differentially expressed genes in AAD have been recognized, interactions between these genes remain poorly defined. This study was conducted to gain a better understanding of the molecular mechanisms underlying AAD and to support the future development of a clinical test for monitoring patients at high risk. Materials and Methods Aortic tissue was collected from 19 patients with AAD (mean age 61.7 ± 13.1 years), and from eight other patients (mean age 32.9 ± 12.2 years) who carried the mutated gene for Marfan syndrome (MS). Six patients (mean age 56.7 ± 12.3 years) served as the control group. The PIQOR™ Immunology microarray with 1076 probes in quadruplicates was utilized; the differentially expressed genes were analysed in a MedScan search using PathwayAssist software. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and protein analysis were performed. Results Interactions of MS fibrillin-1 (FBN1) in the MedScan pathway analysis showed four genes, fibulin-1 (FBLN1), fibulin-2 (FBLN2), decorin (DCN) and microfibrillar associated protein 5 (MFAP5), which were differentially expressed in all tissue from AAD. The validation of these genes by qRT-PCR revealed a minimum of three-fold downregulation of FBLN1 (0.5 ± 0.4 vs. 6.1 ± 2.3 fold, p = 0.003) and of DCN (2.5 ± 1.0 vs. 8.5 ± 4.7 fold, p = 0.04) in AAD compared to MS and control samples. Conclusions Downregulation of fibrillin-1 (FBN1) may weaken extracellular components in the aorta and/or interfer with the transmission of cellular signals and eventually cause AAD. Additional research on these four identified genes can be a starting point to develop a diagnostic tool.

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MiR-384 is associated with renal damage in lupus nephritis via regulation of TET3 expression

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v19i12.13 ◽

2021 ◽

Vol 19 (12) ◽

pp. 2571-2576

Author(s):

Jun Zhang ◽

Suli Lu ◽

Ting Ding ◽

Haijia Zhao ◽

Dongxing Tang

Keyword(s):

Lupus Nephritis ◽

Serum Creatinine ◽

Renal Damage ◽

Complement C3 ◽

Enzyme Linked Immunosorbent Assay ◽

Serum Complement ◽

Urine Protein ◽

Qrt Pcr ◽

Potential Biomarker ◽

Protein Serum

Purpose: To investigate the correlations between miR-384 expression and renal damage in lupus nephritis (LN).Methods: Lupus nephritis and normal tissues were collected during surgery. The relative miR-384 expression was evaluated by extracting RNA and performing quantitative real time PCR (qRT-PCR) assays. Expression of ten-eleven translocation (TET3) mRNA and protein were measured by qRT-PCR and western blotting, respectively. The 24-h urine protein, serum complement C3, and serum creatinine were determined using commercial enzyme-linked immunosorbent assay (ELISA) kits. TargetScan and luciferase assays were used to validate the binding site for miR-384 and its target mRNA. Relationships among miR-384, TET3, and renal damage were analyzed by Spearman rank-order correlation coefficients.Results: MiR-384 expression increased in LN tissues and was positively correlated with the activity index (AI) and chronicity index of LN, whereas miR-384 expression and serum complement C3 were negatively correlated. Positive correlations were observed between miR-384 expression and 24-h urine protein, serum creatinine, and systemic lupus erythematosus disease AI. TargetScan and luciferaseassays indicated that the TET3 3′-UTR was the direct target of miR-384. MiR-384 upregulation inhibited TET3 mRNA and protein expression, and was negatively associated with renal damage in LN.Conclusion: MiR-384 upregulation contributes to renal damage in LN by targeting the 3′-UTR of TET3 mRNA, suggesting that miR-384 is a potential biomarker and therapeutic target in LN. Keywords: MiR-384, Renal damage, Lupus nephritis, Ten-eleven translocation, TET3

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Ischemia-Modified Albumin As a Marker for Acute Aortic Dissection: A Prospective Observational Study

10.21203/rs.3.rs-588867/v1 ◽

2021 ◽

Author(s):

Yang zhou ◽

Xiangping Chai ◽

Huaping He ◽

Wen Peng ◽

Guifang Yang ◽

...

Keyword(s):

Aortic Dissection ◽

Prospective Observational Study ◽

Acute Aortic Dissection ◽

Area Under The Curve ◽

Cost Effective ◽

Final Diagnosis ◽

Net Benefit ◽

Ischemia Modified Albumin ◽

Potential Biomarker ◽

Cobalt Binding

Abstract Background: Delayed or misdiagnosed aortic dissection can lead to death and morbidity. Ischemia-modified albumin (IMA) measures the cobalt binding capability and has been associated with mortality in patients with acute aortic dissection (AAD). However, it is unknown whether IMA levels can differentiate AAD in patients with chest pains.Methods: A total of 100 suspected AAD patients were enrolled in this study. A cobalt-binding assay was used to determine the plasma IMA levels. In addition, the IMA levels of patients in different groups were compared based on the final diagnosis. Results: IMA levels were significantly higher in the AAD group than in the AMI, PE, and other groups (63.98 ± 14.38, 52.57 ± 9.54, 49.26 ± 10.99, 37.99 ± 6.59, respectively) within 24 hours after the onset of symptoms. The area under the curve (AUC) based on the IMA level was 0.810 (95% CI, 0.708–0.897), and the best threshold of IMA was 59.35 u/ml (specificity, 85.7% and sensitivity, 66%). The decision and clinical impact curves indicated that the IMA had an excellent standardized net benefit and could be suitable for patient diagnosis.Conclusion: IMA is elevated in AAD patients. The IMA levels have better performance for AAD than D-dimer and could be a potential biomarker with rapid and cost-effective diagnostic tests for early diagnosis of AAD. However, large-sample studies are needed to verify the findings.

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Association Among B Lymphocyte Subset and Rheumatoid Arthritis in A Chinese Population

10.21203/rs.3.rs-793561/v1 ◽

2021 ◽

Author(s):

Haiyan You ◽

Mengwei Cheng ◽

Cui Ma ◽

Wenjuan Zheng ◽

Yu Jiang ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Healthy Subjects ◽

B Lymphocyte ◽

Lymphocyte Subsets ◽

Characteristic Curve ◽

Area Under The Curve ◽

Enzyme Linked Immunosorbent Assay ◽

Roc Curve Analysis ◽

Autoantibody Production ◽

Plasma Cytokines

Abstract Background and aim: Autoantibody production are the main risk factors for inflammation of rheumatoid arthritis (RA). This study aimed to investigate differences in B lymphocyte subsets (native B, memory B, and plasmablasts) and several cytokines in RA patients and their correlation with the clinical parameters. Methods In total, 81 RA patients (active RA and inactive RA) and 40 healthy subjects were recruited between September 2018 and October 2020. The distribution of B lymphocyte subsets in peripheral blood samples was measured via flow cytometry and the plasma cytokines were detected by enzyme linked immunosorbent assay. The receiver operating characteristic curve (ROC) was used to evaluate the value of each index for RA diagnosis and activity prediction. Results The percentages of native B and memory B cells in RA patients did not differ significantly from the percentages of those in healthy controls. However, the percentage of plasmablasts in active RA patients was significantly higher compared with healthy subjects and inactive RA patients. The percentage of plasmablasts was significantly related to C reaction protein. ROC curve analysis showed that when the best cutoff value of plasmablasts/B cell was 1.08%, the area under the curve (AUC) for diagnosing APN was 0.831 (95% CI 0.748ཞ0.915), the specificity was 91.4%, and the sensitivity was 67.5%. Conclusion In conclusion, the percentage of plasmablast varies among RA patients in different stages. The percentage of plasmablasts can be used as an early diagnosis marker for RA.

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