scholarly journals Soluble cytotoxic T-lymphocyte–associated antigen 4 (sCTLA-4) as a potential biomarker for diagnosis and evaluation of the prognosis in Glioma

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Jiajia Liu ◽  
Xiaoyi Tian ◽  
Yan Wang ◽  
Xixiong Kang ◽  
Wenqi Song

Abstract Background The cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) is widely considered as a pivotal immune checkpoint molecule to suppress antitumor immunity. However, the significance of soluble CTLA-4 (sCTLA-4) remains unclear in the patients with brain glioma. Here we aimed to investigate the significance of serum sCTLA-4 levels as a noninvasive biomarker for diagnosis and evaluation of the prognosis in glioma patients. Methods In this study, the levels of sCTLA-4 in serum from 50 patients diagnosed with different grade gliomas including preoperative and postoperative, and 50 healthy individuals were measured by an enzyme-linked immunosorbent assay (ELISA). And then ROC curve analysis and survival analyses were performed to explore the clinical significance of sCTLA-4. Results Serum sCTLA-4 levels were significantly increased in patients with glioma compared to that of healthy individuals, and which was also positively correlated with the tumor grade. ROC curve analysis showed that the best cutoff value for sCTLA-4 for glioma is 112.1 pg/ml, as well as the sensitivity and specificity with 82.0 and 78.0%, respectively, and a cut-off value of 220.43 pg/ml was best distinguished in patients between low-grade glioma group and high-grade glioma group with sensitivity 73.1% and specificity 79.2%. Survival analysis revealed that the patients with high sCTLA-4 levels (> 189.64 pg/ml) had shorter progression-free survival (PFS) compared to those with low sCTLA-4 levels (≤189.64 pg/ml). In the univariate analysis, elder, high-grade tumor, high sCTLA-4 levels and high Ki-67 index were significantly associated with shorter PFS. In the multivariate analysis, sCTLA-4 levels and tumor grade remained an independent prognostic factor. Conclusion These findings indicated that serum sCTLA-4 levels play a critical role in the pathogenesis and development of glioma, which might become a valuable predictive biomarker for supplementary diagnosis and evaluation of the progress and prognosis in glioma.

2012 ◽  
Vol 25 (1) ◽  
pp. 67-74 ◽  
Author(s):  
M. Scarpelli ◽  
R. Mazzucchelli ◽  
F. Barbisan ◽  
A. Santinelli ◽  
A. Lopez-Beltran ◽  
...  

Prostate Tumour Overexpressed-1 (PTOV1) was recently identified as a novel gene and protein during a differential display screening for genes overexpressed in prostate cancer (PCa). α-Methyl-CoA racemose (AMACR) mRNA was identified as being overexpressed in PCa. PTOV1 and racemase were immunohistochemically evaluated in PCa, high-grade prostatic intraepithelial neoplasia (HGPIN), atrophy and normal-looking epithelium (NEp) in 20 radical prostatectomies (RPs) with pT2a Gleason score 6 prostate cancer with the aim of analyzing the differences in marker expression between PTOV1 and AMACR. The level of expression of PTOV1 and AMACR increased from NEp and atrophy through HGPIN, away from and adjacent to prostate cancer, to PCa. With the ROC curve analysis the overall accuracy in distinguishing PCa vs HGPIN away from and adjacent to cancer was higher for AMACR than for PTOV1. In conclusion, AMACR can be considered a more accurate marker than PTOV1 in the identification of HGPIN and of PCa. However, PTOV1 may aid in the diagnosis of PCa, at least to supplement AMACR as another positive marker of carcinoma and to potentially increase diagnostic accuracy.


2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S273-S273
Author(s):  
Amy C Sherman ◽  
Teresa C Smith ◽  
Daniel Espinoza ◽  
Yerun Zhu ◽  
Jessica Howard-Anderson ◽  
...  

Abstract Background Sensitive and specific SARS-CoV-2 antibody diagnostics are urgently needed to estimate the seroprevalence of SARS-CoV-2 infection in both the general population and special risk groups. Moreover, validated serologic assays are critical to understanding immunity to SARS-CoV-2 infection over time and identifying correlates of protection. Methods An enzyme-linked immunosorbent assay (ELISA) protocol to detect antibodies (IgG) that bind the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein was validated and ROC curve analysis performed by testing a large panel of pre-pandemic sera (n=162) and convalescent sera from RT-PCR-confirmed COVID-19 cases (n=60). We then applied this test in two cohorts: 1) Healthcare personnel (HCP) that were enrolled in a longitudinal surveillance cohort just after peak local transmission and 2) Mildly ill patients being tested for SARS-CoV-2 infection by RT-PCR from NP swabs in an ambulatory testing clinic. Demographics of mildly symptomatic patients tested for SARS-CoV-2 with RT-PCR Results ROC curve analysis yielded an AUC of 0.9953, with a sensitivity and specificity at 91.67% and 99.38% at the optimal OD normalization threshold of 0.20. In 240 HCP surveilled at enrollment, 5.83% had positive IgG results. Of 19 symptomatic patients who presented to the ambulatory clinic, 5/19 had a positive PCR. In convalescence (13–74 days post symptom onset), 3 of those 5 were positive for IgG. Validation of the SARS-CoV-2 RBD ELISA ROC Curve Analysis Conclusion We demonstrated high sensitivity and specificity of the SARS-CoV-2 RBD ELISA. This simple assay is an efficient way to track seroconversion and duration of antibody responses to SARS-CoV-2 for different populations, particularly since RBD-binding antibodies have been shown to correlate with neutralization activity and may be useful to determine protective immunity following natural infection or vaccination. Ongoing work will assess variation in magnitude, character and duration of antibody responses in key populations and seek to maximize deployability of large-scale SARS-CoV-2 serology. Disclosures Jessica Howard-Anderson, MD, MSc, Antibacterial Resistance Leadership Group (ARLG) (Other Financial or Material Support, The ARLG fellowship provides salary support for ID fellowship and mentored research training) Nadine Rouphael, MD, Lilly (Grant/Research Support)Merck (Grant/Research Support)Pfizer (Grant/Research Support)Quidel (Grant/Research Support)Sanofi Pasteur (Grant/Research Support)


2019 ◽  
Author(s):  
Jing Li ◽  
Min Ming ◽  
Yonghong Han

Abstract Background This study aimed to investigate the predictive value of JNK pathway-associated phosphatase (JKAP) level for severe acute pancreatitis (SAP) risk, and its association with disease severity, inflammation and in-hospital mortality in SAP patients. Methods Our study recruited 50 SAP patients, 50 moderate-severe acute pancreatitis (MSAP) patients, 50 mild acute pancreatitis (MAP) patients and 50 healthy controls. And the serum samples were obtained from all acute pancreatitis patients within 24 hours after admission and from health controls at their enrollment to detect JKAP level by enzyme-linked immunosorbent assay. Results JKAP level was decreased in SAP patients compared with healthy controls, MSAP and MAP patients. And receiver operating characteristics (ROC) curve analysis revealed that JKAP could not only distinguish SAP patients from healthy controls (AUC: 0.914, 95%CI: 0.857-0.971), but also differentiate SAP patients from MAP patients (AUC: 0.869, 95%CI: 0.802-0.937) and MSAP patients (AUC: 0.712, 95%CI: 0.610-0.813). In SAP patients, JKAP was negatively correlated with Ranson score, acute physiology and chronic health care evaluation II (APACEH II) score, sequential organ failure assessment (SOFA) score and C-reactive protein (CRP). And lower JKAP level, higher CRP level, Ranson score, APACEH II score and SOFA score were associated with increased in-hospital mortality in SAP patients. Additionally, ROC curve analysis showed that JKAP could predict decreased in-hospital mortality in SAP patients (AUC: 0.720, 95%CI: 0.526-0.914). Conclusions JKAP might serve as a biomarker for disease risk and management for SAP.


2020 ◽  
Vol EJMM29 (4) ◽  
pp. 9-15
Author(s):  
Rania A. El-Kady ◽  
Mohammed M. El-Naggar ◽  
ehab A. Abd El-Shakour ◽  
Monir H. Bahgat

Background: Hepatocellular carcinoma (HCC) is amongst the most common malignant tumors that carries a poor prognosis. Clinically, alpha-fetoprotein (AFP) is the most extensively used serum biomarker for diagnosing HCC. Objectives: The current study was conducted to explore the diagnostic value of serum levels of alpha-fetoprotein-L3 (AFP-L3) and Golgi protein 73 (GP73) regarding HCC, and to determine the diagnostic accuracy of these biomarkers when used individually as well as in combination with AFP. Methodology: Blood samples were collected from 50 patients with HCV-related cirrhosis (25 subjects with HCC and 25 without HCC) recruited from the outpatient clinics of the Specialized Internal Medicine Hospital, Mansoura University, Egypt. Serum concentrations of AFP-L3 and GP73 were evaluated using enzyme-linked immunosorbent assay (ELISA). Diagnostic performance of AFP-L3 and GP73 was determined by receiver operating characteristic (ROC) curve analysis. Results: Overall, the median serum level of AFP-L3 was higher in the HCC group compared to the cirrhotic group (p=0.05). Moreover, a statistically-significant difference was observed between the median serum value of GP73 in HCC patients compared to those with cirrhosis (p < 0.001). The ROC curve analysis showed that the area under the ROC curve (AUROC) values for AFP, AFP-L3 and GP73 were 0.88, 0.67 and 0.83, respectively. Of the 3 biomarkers, GP73 demonstrated the highest sensitivity (88%). The AUROC for AFP and AFP-L3 combination was 0.85, whereas that for AFP and GP73 was 0.90. Conclusion: Our findings indicate that GP73 is more sensitive than AFP and AFP-L3 in diagnosing HCC. Furthermore, the combined determination of GP73 and AFP could improve the diagnostic ability of HCC.


2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Beata Smok ◽  
Krzysztof Domagalski ◽  
Małgorzata Pawłowska

Purpose. The aim of this study was to evaluate the diagnostic and prognostic value of IL-6 and sTREM-1 in the course of SIRS and sepsis in children with reference to routinely used CRP and PCT. Methods. A prospective study included 180 patients at the ages from 2 months to 18 years hospitalized due to fever from November 2015 to January 2017. Forty-nine children without fever hospitalized due to noninfectious causes formed the control group. IL-6 and sTREM-1 serum concentrations were assessed with the enzyme-linked immunosorbent assay method. Results. The mean serum concentrations of all the analyzed biomarkers were statistically significantly higher in the study group compared to the control group. Mean IL-6, sTREM-1, and PCT serum concentrations were statistically significantly higher in the group of patients with SIRS/sepsis compared to the group of feverish patients without diagnosed SIRS (N-SIRS). Based on the ROC curve analysis, it was shown that of all the biomarkers tested, only two—IL-6 and procalcitonin—had potential usefulness in the diagnosis of SIRS/sepsis in children with fever. Conclusion. Elevated levels of IL-6 and PCT are important risk factors for the development of SIRS/sepsis in children with fever. It seems that elevated IL-6 baseline serum level may predict a more severe course of febrile illness in children, because based on the ROC curve analysis, it was found that IL-6 is a statistically significant prognostic marker of prolonged fever≥3 days and prolonged hospitalization>10 days. The assessment of the usefulness of sTREM-1 in the diagnosis of SIRS/sepsis in feverish children requires further research.


Neurosurgery ◽  
2004 ◽  
Vol 55 (3) ◽  
pp. 562-568 ◽  
Author(s):  
Einat Peles ◽  
Zvi Lidar ◽  
Amos J. Simon ◽  
Rachel Grossman ◽  
Dvora Nass ◽  
...  

Abstract OBJECTIVE: Gliomas account for most primary brain tumors in adults, and survival correlates with the grade and vascularity of the tumor. The degree of tumor-related angiogenesis seems to be a significant predictor of tumor progression, recurrence, and metastatic spread in a variety of malignant diseases, including brain tumors. Our study's objective was to quantify the levels of two angiogenic factors, basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF), in the cerebrospinal fluid (CSF) and serum of patients with gliomas and to correlate these levels with tumor grade, vascularity, and overall survival. METHODS: Twenty-six patients with the diagnosis of cerebral glioma (19 high-grade, 7 low-grade) comprised the study group. Ten patients with communicating hydrocephalus served as controls. Levels of VEGF and bFGF in the CSF and serum were determined using enzyme-linked immunosorbent assay analysis. Tumor vascularity was graded qualitatively using immunohistochemical staining for CD34. Nonparametric statistical techniques were used for data analysis. RESULTS: Median levels of bFGF and VEGF in the CSF were significantly higher in patients with high-grade glioma as compared with patients with low-grade glioma or hydrocephalus (bFGF levels, 52, 26, and 24 ng/ml, respectively, P &lt; 0.0001; VEGF levels, 17.6, 7.2, and 8.3 ng/ml, respectively, P &lt; 0.005). A significant correlation was found comparing CSF levels of bFGF with levels of VEGF (P &lt; 0.001). The levels of the angiogenic factors in the CSF correlated with the degree of tumor vascularity and were adversely associated with patient survival. Serum levels of the angiogenic factors showed no correlation to tumor grade, vascularity, or survival. CONCLUSION: Our data suggest that CSF levels of bFGF and VEGF may serve as an additional marker for tumor grading and vascularity and may help predict survival.


2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Siyu Wu ◽  
Wanchan Peng ◽  
Yunli Zhang ◽  
Jingjing Guo ◽  
Jinfang Fu ◽  
...  

Abstract Background Polymorphonuclear (PMN) elastase plays an important role in a variety of inflammatory disorders. Our aim was to analyse PMN elastase in idiopathic inflammatory myopathies (IIMs) and its association with disease activity. Methods PMN elastase levels were measured using enzyme-linked immunosorbent assay in serum samples obtained from 74 patients with myositis (58 with dermatomyositis [DM] and 16 with polymyositis [PM]) and 22 healthy controls. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the discriminant capacity of PMN elastase level and PMN elastase-to-neutrophil ratio (ENR) in patients with active and remission myositis. The association of serum PMN elastase level and ENR with disease variables was evaluated in patients with IIMs. The disease specificity of PMN elastase level and ENR was further examined in 60 patients with other systemic autoimmune diseases. Results PMN elastase level and ENR were significantly higher in patients with active IIMs, DM, and PM than in patients with remission. ROC curve analysis revealed that PMN elastase level and ENR both outperformed creatine kinase (CK), the currently used laboratory marker, and strongly discriminated patients with active disease and those with remission of IIMs, DM, and PM (area under the ROC curve [AUC] 0.9, 0.9, and 0.88 for PMN elastase; AUC 0.96, 0.96, and 1.0 for ENR; AUC 0.72, 0.70, and 0.80 for CK, respectively). PMN elastase level and ENR were positively correlated with myositis disease activity assessment, CK, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase, C-reactive protein, and erythrocyte sedimentation rate. PMN elastase level and ENR were higher in the anti-PM-Scl positive myositis group than those in the anti-PM-Scl negative myositis group. Nevertheless, PMN elastase was not a specific disease marker for IIMs when compared with other autoimmune diseases. Conclusions PMN elastase, particularly ENR, were significantly correlated with disease activity and could serve as useful biochemical markers for evaluating the disease activity of patients with IIMs. Thus, they are potentially helpful in monitoring disease progression and guiding treatment.


2010 ◽  
Vol 56 (5) ◽  
pp. 781-788 ◽  
Author(s):  
Rehana S Lovely ◽  
Steven C Kazmierczak ◽  
Joseph M Massaro ◽  
Ralph B D'Agostino ◽  
Christopher J O'Donnell ◽  
...  

Abstract Background: Studies of disease associations with γ′ fibrinogen, a newly emerging risk factor for cardiovascular disease, have been hampered by the lack of a standardized and well-characterized assay. Methods: We developed an immunometric technique to measure γ′ fibrinogen concentrations in plasma and studied the clinical utility of this test in samples from healthy individuals enrolled in the Framingham Offspring Study and in a separate case/control study of coronary artery disease (CAD). Monoclonal antibody 2.G2.H9, specific for the unique carboxyl terminal peptide of the fibrinogen γ′ chain, was used as capture antibody. Sheep antihuman fibrinogen/horseradish peroxidase conjugate was used for detection, with 3,3′,5,5′-tetramethylbenzidine as substrate. We evaluated the linearity, imprecision, analytical specificity, and lower limit of quantification of the assay. We determined the reference interval for γ′ fibrinogen in healthy individuals from the Framingham Offspring Study (n = 2879) and quantified associations between γ′ fibrinogen and cardiovascular disease risk factors. The sensitivity and specificity of γ′ fibrinogen in evaluating CAD patients (n = 133) was determined with ROC curve analysis. Results: The γ′ fibrinogen ELISA had within-run CVs of 13.4% at 0.127 g/L and 4.8% at 0.416 g/L. The limit of quantification at an imprecision of 20% was 0.10 g/L. The reference interval for healthy individuals was 0.088–0.551 g/L. ROC curve analysis of results from patients with CAD yielded an area under the curve of 0.76, with a diagnostic accuracy of 0.78 at a decision threshold of 0.30 g/L. Conclusions: γ′ Fibrinogen shows excellent utility for cardiovascular risk analysis.


2021 ◽  
Vol 10 (1-2) ◽  
pp. 33-39
Author(s):  
Sultana Israt Jahan ◽  
Shah Md Badruddoza ◽  
SM Asafudullah ◽  
Md Nurul Amin

Background & objective: The role Ki-67 as a prognostic marker has been studied in many cancers in many studies. However, only few studies reported the prognostic role of Ki-67 in colorectal carcinoma (CRC) with contradictory opinions. The present study was undertaken to assess the Ki-67 proliferation index (PI) in tissue sections of CRC and to investigate the relationship between the proliferative activity and histological type, grade and stage of the tumour. Methods: The present cross-sectional descriptive study was conducted in the Department of Pathology, Rajshahi Medical College, Rajshahi over a period of two years from September 2017 to August 2019. All clinically suspected cases of CRC and later confirmed by histopathology were the study population. A total 44 such cases were included in the study. Tissue sections from 44 formalin-fixed and paraffin-embedded tumor specimens were examined at the Department of Pathology of Rajshahi Medical College, Rajshahi. The cases were histologically classified, graded (WHO) and staged according to TNM and modified Dukes’ staging system. Ki-67 proliferation index was calculated immunohistochemically using the monoclonal antibody MIB-1, and were studied under light microscope. Expression of Ki-67 was calculated as a percentage of labeled nuclei per 500 cells counted in consecutive five high-power fields in the most reactive areas of the slides. The staining results were categorized into groups using a cut-off value of Ki-67 determined by ROC curve analysis. Results: In the present study the cases with high Ki-67 PI were significantly associated with high grade colorectal carcinoma (p = 0.005). TNM Stage-II and Stage-III tumours were more likely to be associated with high Ki-67 PI than those with low Ki-67 PI (p < 0.001). A significant association was observed between Ki-67 immuno-expression and modified Dukes’ staging of the tumours with Stage C being highly associated with high Ki-67 PI (p < 0.001). But histologic tumor type (mucinous and non-mucinous) was not found to be associated with Ki-67 proliferation index. Based on Receiver Operating Characteristic (ROC) curve analysis tumors with nuclear immunoreactivity ≥ 25% were considered as high proliferation index (PI) and < 25% as low PI. The Ki-67 at a cut-off value of >25% had high sensitivity (85.7%) in differentiating high grade CRC from the low-grade tumors but its specificity was moderate (67.6%) with overall diagnostic accuracy being 70.5%. Conclusion: The study concluded that cases with high Ki-67 PI are significantly associated with high grade CRC (poorly differentiated) than the cases with low grade CRC (well and moderately differentiated). TNM Stage-II & Stage-III and modified Dukes’ stage C also more often tend to be associated with high Ki-67 PI than with low Ki-67 PI. Ibrahim Card Med J 2020; 10 (1&2): 33-39


2021 ◽  
Vol 28 (Supplement_1) ◽  
Author(s):  
M Santos ◽  
S Paula ◽  
I Almeida ◽  
H Santos ◽  
H Miranda ◽  
...  

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Patients (P) with acute heart failure (AHF) are a heterogeneous population. Risk stratification at admission may help predict in-hospital complications and needs. The Get With The Guidelines Heart Failure score (GWTG-HF) predicts in-hospital mortality (M) of P admitted with AHF. ACTION ICU score is validated to estimate the risk of complications requiring ICU care in non-ST elevation acute coronary syndromes. Objective To validate ACTION-ICU score in AHF and to compare ACTION-ICU to GWTG-HF as predictors of in-hospital M (IHM), early M [1-month mortality (1mM)] and 1-month readmission (1mRA), using real-life data. Methods Based on a single-center retrospective study, data collected from P admitted in the Cardiology department with AHF between 2010 and 2017. P without data on previous cardiovascular history or uncompleted clinical data were excluded. Statistical analysis used chi-square, non-parametric tests, logistic regression analysis and ROC curve analysis. Results Among the 300 P admitted with AHF included, mean age was 67.4 ± 12.6 years old and 72.7% were male. Systolic blood pressure (SBP) was 131.2 ± 37.0mmHg, glomerular filtration rate (GFR) was 57.1 ± 23.5ml/min. 35.3% were admitted in Killip-Kimball class (KKC) 4. ACTION-ICU score was 10.4 ± 2.3 and GWTG-HF was 41.7 ± 9.6. Inotropes’ usage was necessary in 32.7% of the P, 11.3% of the P needed non-invasive ventilation (NIV), 8% needed invasive ventilation (IV). IHM rate was 5% and 1mM was 8%. 6.3% of the P were readmitted 1 month after discharge. Older age (p &lt; 0.001), lower SBP (p = 0,035) and need of inotropes (p &lt; 0.001) were predictors of IHM in our population. As expected, patients presenting in KKC 4 had higher IHM (OR 8.13, p &lt; 0.001). Older age (OR 1.06, p = 0.002, CI 1.02-1.10), lower SBP (OR 1.01, p = 0.05, CI 1.00-1.02) and lower left ventricle ejection fraction (LVEF) (OR 1.06, p &lt; 0.001, CI 1.03-1.09) were predictors of need of NIV. None of the variables were predictive of IV. LVEF (OR 0.924, p &lt; 0.001, CI 0.899-0.949), lower SBP (OR 0.80, p &lt; 0.001, CI 0.971-0.988), higher urea (OR 1.01, p &lt; 0.001, CI 1.005-1.018) and lower sodium (OR 0.92, p = 0.002, CI 0.873-0.971) were predictors of inotropes’ usage. Logistic regression showed that GWTG-HF predicted IHM (OR 1.12, p &lt; 0.001, CI 1.05-1.19), 1mM (OR 1.10, p = 1.10, CI 1.04-1.16) and inotropes’s usage (OR 1.06, p &lt; 0.001, CI 1.03-1.10), however it was not predictive of 1mRA, need of IV or NIV. Similarly, ACTION-ICU predicted IHM (OR 1.51, p = 0.02, CI 1.158-1.977), 1mM (OR 1.45, p = 0.002, CI 1.15-1.81) and inotropes’ usage (OR 1.22, p = 0.002, CI 1.08-1.39), but not 1mRA, the need of IV or NIV. ROC curve analysis revealed that GWTG-HF score performed better than ACTION-ICU regarding IHM (AUC 0.774, CI 0.46-0-90 vs AUC 0.731, CI 0.59-0.88) and 1mM (AUC 0.727, CI 0.60-0.85 vs AUC 0.707, CI 0.58-0.84). Conclusion In our population, both scores were able to predict IHM, 1mM and inotropes’s usage.


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