Urinary APE1/Ref-1: A Potential Bladder Cancer Biomarker

Bladder cancer (BCa) is one of the most common urothelial cancers with still noticeable incidence rate. Early detection of BCa is highly correlated with successful therapeutic outcomes. We previously showed that apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) was expressed at an increased level in the serum of BCa patients when compared to the level in healthy controls. In this study, we investigated whether urinary APE1/Ref-1 was also elevated in patients with BCa. In this case-control study, voided urine was collected from 277 subjects including 169 BCa patients and 108 non-BCa controls. Urinary APE1/Ref-1 level was assessed by enzyme-linked immunosorbent assay (ELISA). APE1/Ref-1 levels were significantly elevated in BCa patients relative to levels in non-BCa controls and were correlated with tumor grade and stage. Urinary APE1/Ref-1 levels were also higher in patients with recurrence history of BCa. The receiver operating characteristics (ROC) curve of APE1/Ref-1 showed an area under the curve of 0.83, indicating the reliability and validity of this biomarker. The optimal combination of sensitivity and specificity was determined to be 82% and 80% at a cut-off value of 0.376 ng/100 μL for detection of APE1/Ref-1 in urine. In conclusion, urinary APE1/Ref-1 levels measured from noninvasively obtained body fluids would be clinically applicable for diagnosis of BCa.

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Downregulation of Urinary microRNA-200c acts as a Promising Novel Bio-marker in the Diagnosis of Patients With Bladder Cancer

10.21203/rs.3.rs-91603/v1 ◽

2020 ◽

Author(s):

Hao Zi ◽

Wen-Lin Tao ◽

Lei Gao ◽

Zhao-Hua Yu ◽

Xiao-Dong Bai ◽

...

Keyword(s):

Bladder Cancer ◽

Cancer Patients ◽

Roc Curve ◽

Area Under The Curve ◽

Tumor Grade ◽

Healthy Controls ◽

Strongly Correlated ◽

Operating Characteristics ◽

Diagnostic Capacity ◽

Pcr Method

Abstract BackgroundMicroRANs (miRNAs) have been reported to be involved in various human cancers. The aim of this study was to explore the diagnostic performance of urine miR-200c in bladder cancer. MethodsQuantitative real-time polymerase chain reaction (qRT-PCR) method was applied to measure the relative expression of urine miR-200c in bladder cancer patients. The relationship between urine miR-200c level and clinicopathological factors was analyzed using χ2 test. The diagnostic capacity of urine miR-200c was calculated using the receiver operating characteristics (ROC) curve analysis.ResultsUrinary level of miR-200c was significantly reduced in bladder cancer patients compared with healthy controls (P=0.000). Furthermore, urine miR-200c expression was strongly correlated with histologic grade (P=0.019), tumor grade (P=0.003), and lymph node metastasis (P=0.001). ROC curve showed that urine miR-200c could distinguish bladder cancer patients from healthy controls with an area under the curve of 0.844. The cutoff value of 1.235, with the sensitivity of 89.0% and the specificity of 70.7% respectively.ConclusionUrine miR-200c may act as a noninvasive diagnostic biomarker for bladder cancer.

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MicroRNAs Which Can Prognosticate Aggressiveness of Bladder Cancer

Cancers ◽

10.3390/cancers11101551 ◽

2019 ◽

Vol 11 (10) ◽

pp. 1551 ◽

Cited By ~ 3

Author(s):

Edyta Marta Borkowska ◽

Tomasz Konecki ◽

Michał Pietrusiński ◽

Maciej Borowiec ◽

Zbigniew Jabłonowski

Keyword(s):

Bladder Cancer ◽

Area Under The Curve ◽

Roc Curves ◽

Control Group ◽

Low Grade ◽

Operating Characteristics ◽

High Death Rate ◽

Biological Potential ◽

High Death ◽

Muscle Invasive

Bladder cancer (BC) is still characterized by a very high death rate in patients with this disease. One of the reasons for this is the lack of adequate markers which could help determine the biological potential of the tumor to develop into its invasive stage. It has been found that some microRNAs (miRNAs) correlate with disease progression. The purpose of this study was to identify which miRNAs can accurately predict the presence of BC and can differentiate low grade (LG) tumors from high grade (HG) tumors. The study included 55 patients with diagnosed bladder cancer and 30 persons belonging to the control group. The expression of seven selected miRNAs was estimated with the real-time PCR technique according to miR-103-5p (for the normalization of the results). Receiver operating characteristics (ROC) curves and the area under the curve (AUC) were used to evaluate the feasibility of using selected markers as biomarkers for detecting BC and discriminating non-muscle invasive BC (NMIBC) from muscle invasive BC (MIBC). For HG tumors, the relevant classifiers are miR-205-5p and miR-20a-5p, whereas miR-205-5p and miR-182-5p are for LG (AUC = 0.964 and AUC = 0.992, respectively). NMIBC patients with LG disease are characterized by significantly higher miR-130b-3p expression values compared to patients in HG tumors.

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Serum CYR61 As A Potential Biomarker for The Diagnosis of Esophagogastric Junction Tumor

Bioscience Reports ◽

10.1042/bsr20204117 ◽

2021 ◽

Author(s):

Ling-Yu Chu ◽

Jian-Yuan Zhou ◽

Yi-Xuan Zhao ◽

Yan-Ting Ou ◽

Tian Yang ◽

...

Keyword(s):

Early Stage ◽

Area Under The Curve ◽

Serum Levels ◽

Enzyme Linked Immunosorbent Assay ◽

Operating Characteristics ◽

Tumor Patients ◽

Chi Square ◽

Potential Biomarker ◽

The Difference ◽

Normal Controls

Background：Esophagogastric junction tumor (EGJ) is a rare but fatal disease with a rapid rising incidence worldwide in the late 20 years, and it lacks a convenient and safe method for diagnosis. This study aimed to evaluate the potential of serum CYR61 as a biomarker for the diagnosis of EGJ tumor. Methods: Enzyme-linked immunosorbent assay (ELISA) was used to estimate CYR61 levels in sera of 152 EGJ tumor patients and 137 normal controls. Receiver operating characteristics (ROC) was carried out to evaluate the diagnostic accuracy. The Mann–Whitney’s U test was used to compare the difference of serum levels of CYR61 between groups. And chi-square tests were employed to estimate the correlation of the positive rate of serum CYR61 between/among subgroups. Results: Serum CYR61 levels were statistically lower in EGJ tumor and early-stage EGJ tumor patients than those in normal controls (P<0.0001). The sensitivity, specificity, and the area under the curve (AUC) of this biomarker in EGJ tumor were 88.2%, 43.8% and 0.691, respectively, and those for early stage of EGJ tumor were 80.0%, 66.4% and 0.722, respectively. Analyses showed that there was no correlation between the clinical data and the levels of CYR61 (P>0.05). Conclusion: This study showed that CYR61 might be a potential biomarker to assist the diagnosis of EGJ tumor.

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ANTINUCLEAR ANTIBODIES IN PATIENTS WITH UNEXPLAINED RECURRENT ABORTIONS

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2017.v10i8.18343 ◽

2017 ◽

Vol 10 (8) ◽

pp. 256 ◽

Cited By ~ 1

Author(s):

Anupriya Asaithambi ◽

Manjula Gunasekaran ◽

Manivelan S ◽

Palaniappan Nainar

Keyword(s):

Pregnant Women ◽

Antinuclear Antibodies ◽

Antibody Test ◽

Enzyme Linked Immunosorbent Assay ◽

Cell Substrate ◽

Simple Alternative ◽

History Of ◽

Recurrent Abortions ◽

Control Study ◽

Indirect Fluorescence Antibody

Objective:This study aims to determine the prevalence of antinuclear antibodies in pregnant women with bad obstetric history (BOH) against healthy multigravid women in and around Tirunelveli districtMethods: This is a case-control study comprising 60 antenatal women with BOH against 60 multiparous pregnant women with no history of abortions. Antinuclear antibodies (ANA) were detected using indirect immunofluorescence with Hep-2 cell substrate, and enzyme-linked immunosorbent assay (ELISA).Results: Among BOH cases 19 (82.6%), 18 (78.26%) were positive by ELISA and indirect fluorescence antibody test (IFAT) method, respectively. Among controls, 4(17.39%) and 5(21.73%) individuals were positive by ELISA and IFAT methods, respectively. Of the 18 positives, homogenous pattern was most common followed by anticentromere pattern, fine speckled and coarse speckled patternConclusion: IFAT is considered to be gold standard in the diagnosis of autoimmune disorders, but ELISA appears to be a suitable simple alternative for testing rheumatological disorders.

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Comparison of Commercial ELISA Kits, a Prototype Multiplex Electrochemoluminescent Assay, and a Multiplex Bead-Based Immunoassay for Detecting a Urine-Based Bladder-Cancer-Associated Diagnostic Signature

Diagnostics ◽

10.3390/diagnostics9040166 ◽

2019 ◽

Vol 9 (4) ◽

pp. 166

Author(s):

Hideki Furuya ◽

Ian Pagano ◽

Keanu Chee ◽

Takashi Kobayashi ◽

Regan S. Wong ◽

...

Keyword(s):

Bladder Cancer ◽

Matrix Metalloproteinase ◽

Protein Array ◽

Enzyme Linked Immunosorbent Assay ◽

Operating Characteristics ◽

Predictive Values ◽

Multiplex Assays ◽

Diagnostic Signature ◽

Technical Specifications ◽

Multiplex Bead

The ability to accurately measure multiple proteins simultaneously in a single assay has the potential to markedly improve the efficiency of clinical tests composed of multiple biomarkers. We investigated the diagnostic accuracy of the two multiplex protein array platforms for detecting a bladder-cancer-associated diagnostic signature in samples from a cohort of 80 subjects (40 with bladder cancer). Banked urine samples collected from Kyoto and Nara Universities were compared to histologically determined bladder cancer. The concentrations of the 10 proteins (A1AT; apolipoprotein E—APOE; angiogenin—ANG; carbonic anhydrase 9—CA9; interleukin 8—IL-8; matrix metalloproteinase 9—MMP-9; matrix metalloproteinase 10—MMP10; plasminogen activator inhibitor 1—PAI-1; syndecan—SDC1; and vascular endothelial growth factor—VEGF) were monitored using two prototype multiplex array platforms and an enzyme-linked immunosorbent assay (ELISA) according to the manufacturer’s technical specifications. The range for detecting each biomarker was improved in the multiplex assays, even though the lower limit of quantification (LLOQ) was typically lower in the commercial ELISA kits. The area under the receiver operating characteristics (AUROC) of the prototype multiplex assays was reported to be 0.97 for the multiplex bead-based immunoassay (MBA) and 0.86 for the multiplex electrochemoluminescent assay (MEA). The sensitivities and specificities for MBA were 0.93 and 0.95, respectively, and for MEA were 0.85 and 0.80, respectively. Accuracy, positive predictive values (PPV), and negative predictive values (NPV) for MBA were 0.94, 0.95, and 0.93, respectively, and for MEA were 0.83, 0.81, and 0.84, respectively. Based on these encouraging preliminary data, we believe that a multiplex protein array is a viable platform that can be utilized as an efficient and highly accurate tool to quantitate multiple proteins within biologic specimens.

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Evaluation of cerebral glioma using 3T diffusion kurtosis tensor imaging and the relationship between diffusion kurtosis metrics and tumor cellularity

Journal of International Medical Research ◽

10.1177/0300060517712654 ◽

2017 ◽

Vol 45 (4) ◽

pp. 1347-1358 ◽

Cited By ~ 8

Author(s):

Chong Qi ◽

Song Yang ◽

Lanxi Meng ◽

Huiyuan Chen ◽

Zhenlan Li ◽

...

Keyword(s):

Mean Diffusivity ◽

Area Under The Curve ◽

Tumor Grade ◽

Superior Performance ◽

Cerebral Glioma ◽

Operating Characteristics ◽

Significant Difference ◽

Characteristics Analysis ◽

Sensitivity Specificity ◽

Diffusion Kurtosis

Purpose To evaluate the clinical utility of diffusion kurtosis tensor imaging in the characterization of cerebral glioma and investigate correlations between diffusion and kurtosis metrics with tumor cellularity. Materials and Methods A group of 163 patients (age: 40.5 ± 11.5 years) diagnosed with cerebral glioma underwent diffusion kurtosis tensor imaging with a 3 T scanner. Diffusion and kurtosis metrics were measured in the solid part of tumors, and their abilities to distinguish between tumor grades was evaluated. In addition, we analyzed correlations between the metrics and tumor cellularity. Results Mean kurtosis (MK) revealed a significant difference between each pair of tumor grades ( P < 0.05) and produced the best performance in a receiver operating characteristics analysis (area under the curve [AUC] = 0.89, sensitivity/specificity = 83.3/90). In contrast, mean diffusivity (MD) revealed a significant difference only for tumor grade II versus IV ( P < 0.05). No significant differences between grades were detected with fractional anisotropy (FA; P > 0.05). Thus, kurtosis metrics exhibited a positive and strong correlation with tumor cellularity, while MD exhibited a negative or weak correlation with tumor cellularity. Conclusion Diffusion kurtosis metrics, particularly MK, demonstrated superior performance in distinguishing cerebral glioma of different grades compared with conventional diffusion metrics, and were closely associated with tumor cellularity.

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Correlation of abnormal upper tract cytology and tumor histology in patients who have undergone a nephroureterectomy for urothelial carcinoma with disease recurrence in the bladder.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.6_suppl.288 ◽

2013 ◽

Vol 31 (6_suppl) ◽

pp. 288-288

Author(s):

Einar Freyr Sverrisson ◽

Timothy Kim ◽

Patrick Espiritu ◽

Wade Jeffers Sexton ◽

Julio Pow-Sang ◽

...

Keyword(s):

Bladder Cancer ◽

Previous History ◽

Tumor Grade ◽

Disease Recurrence ◽

Intravesical Therapy ◽

Prior History ◽

Upper Tract ◽

History Of ◽

One Year ◽

Bladder Recurrence

288 Background: 15-50% of patients with upper tract urothelial carcinomas (UTUC) will have a bladder recurrence. Abnormal upper tract cytology (UTC) is an indicator of higher grade tumors but has not been associated with bladder recurrence. We were interested in investigating the role of UTC as a predictor of bladder cancer recurrences in patients with no prior history of bladder cancer presenting with UTUC. Methods: Of 67 patients who had an UTC collected prior to their nephroureterectomy (NU) in 2004-2012, we identified 17 patients with a recurrent disease in the bladder who met the criteria of having no previous history of bladder cancer at the time of their NU. UTC and histology were reviewed and analyzed with the bladder pathology data. Positive or suspicious cytology was defined as abnormal and atypical or reactive as benign. Results: 15 (88%) of 17 patients (11 men and 6 women) who met our criteria were diagnosed with bladder cancer within one year after their NU (average 7.5 months (range 2-26)). 10 (59%) of 17 patients had abnormal UTC with a calculated sensitivity and specificity of 59% and 22%, respectively. 7 (70%) of 10 patients with abnormal UTC compared to 5 (71%) of 7 patients with benign cytology had high grade (HG) bladder cancer (p=1.0). Muscle invasive tumors were found in 5 (29%) of 17 patients and 3 (60%) of those had abnormal UTC. All six women had HG bladder cancer compared to 6 of 10 men (p=0.23). HG tumors were slightly more common in the bladder compared to the upper tract (75% vs 65%, p=0.70) and 14 (87.5%) of 16 bladder tumors had the same tumor grade in the upper tract. Conclusions: Abnormal UTC is a poor predictor of bladder recurrence in patients with a history of UTUC. The majority of patients who developed bladder recurrence presented within one year from NU with HG disease which underscores the importance of aggressive surveillance and the consideration of prophylactic intravesical therapy at the time of NU in this patient cohort.

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Can Aspirin Use Be Associated With the Risk or Prognosis of Bladder Cancer? A Case-Control Study and Meta-analytic Assessment

Frontiers in Oncology ◽

10.3389/fonc.2021.633462 ◽

2021 ◽

Vol 11 ◽

Author(s):

Bo Fan ◽

Alradhi Mohammed ◽

Yuanbin Huang ◽

Hong Luo ◽

Hongxian Zhang ◽

...

Keyword(s):

Overall Survival ◽

Bladder Cancer ◽

Case Control Study ◽

Meta Analysis ◽

Case Control ◽

Female Patients ◽

Kaplan Meier ◽

History Of ◽

The Impact ◽

Control Study

Aspirin, widely used to prevent cardiovascular disease, had been linked to the incidence of bladder cancer (BCa). Existing studies focusing on Chinese populations are relatively rare, especially for Northeast China. Meanwhile, relevant studies on the effects of aspirin on the occurrence or prognosis of BCa are inconsistent or even controversial. First, in the case control study, logistic regression analysis was used to investigate the association between aspirin intake and risk of BCa including 1121 patients with BCa and the 2242 controls. Subsequently, Kaplan-Meier curve and Cox regression analyses were applied to explore the association between aspirin intake and clinicopathological factors which may predict overall survival (OS) and recurrence-free survival (RFS) of BCa patients. Finally, we quantificationally combined the results with those from the published literature evaluating aspirin intake and its effects on the occurrence, outcome of surgery and prognosis of BCa by meta-analysis up to May 1, 2021.Our case-control study demonstrated that the regular use of aspirin was not associated with a reduced incidence of BCa (P=0.175). Stratified analyses of sex showed that aspirin intake did not lead to a lower risk of BCa in female patients (P=0.063). However, the male population who regularly took aspirin had a lower incidence of BCa (OR=0.748, 95% CI= 0.584-0.958, P=0.021). Subgroup analyses stratified by smoking found a significant reduction in the risk of BCa in current smokers with aspirin intake (OR=0.522, 95% CI=0.342-0.797, P=0.002). In terms of prognosis of BCa, patients with a history of aspirin intake did not had a markedly longer OS or RFS than those with no history of aspirin intake by Kaplan-Meier curves. Stratified analysis by sex showed no correlation between aspirin intake and the recurrence or survival of BCa for either male or female patients. However, in people younger than 68, aspirin intake seemed to have prolonged effects for overall survival (HR=3.876; 95% CI=1.326-11.325, P=0.019). Then, we performed a meta-analysis and the combined results from 19 articles and our study involving more than 39524 BCa cases indicated that aspirin intake was not associated with the occurrence of BCa (P=0.671). Subgroup analysis by whether regular use of aspirin, by the mean duration of use of aspirin, by sex, by smoking exposure, by research region and by study type also supported the above results. In terms of the impact of aspirin intake on the prognosis of patients with BCa, 11 articles and our study involving 8825 BCa cases were eligible. The combined results showed that patients with aspirin intake did not have significantly influence on survival, recurrence, progression and metastasis than those without aspirin intake. On the whole, both our retrospective study and literature meta-analysis suggested a lack of a strong relevant association between the use of aspirin and the incidence or prognosis of BCa. Thus, additional long-term follow-up prospective research is warranted to clarify the association of aspirin with BCa incidence and prognosis.

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Maternal and foetal placental vascular malperfusion in pregnancies with anti-phospholipid antibodies

Rheumatology ◽

10.1093/rheumatology/keaa499 ◽

2020 ◽

Author(s):

Arsenio Spinillo ◽

Camilla Bellingeri ◽

Chiara Cavagnoli ◽

Irene De Maggio ◽

Greta Riceputi ◽

...

Keyword(s):

Case Control Study ◽

Area Under The Curve ◽

First Trimester ◽

Case Control ◽

Healthy Controls ◽

Increased Risk ◽

History Of ◽

First Trimester Of Pregnancy ◽

Penalized Logistic Regression ◽

Control Study

Abstract Objective The objective of the study was to evaluate the rates of pathological placental lesions among pregnant subjects positive for aPL antibodies. Methods We performed a longitudinal case–control study including 27 subjects with primary APS, 51 with non-criteria APS, 24 with aPL antibodies associated with other well-known CTDs enrolled at the end of the first trimester of pregnancy and 107 healthy controls. Results Compared with controls and after correction for multiple comparisons, primary, non-criteria APS and aPL associated to CTD, subjects had lower placental weight, volume and area. After penalized logistic regression analysis to correct for potential confounders, placental lesions suggesting severe maternal vascular malperfusion (MVM) were more common among primary [odds ratio (OR) 11.7 (95% CI 1.3, 108)] and non-criteria APS [OR 8.5 (95% CI 1.6, 45.9)] compared with controls. The risk of foetal vascular malperfusion (FVM) was higher in primary APS [OR 4.5 (95% CI 1.2, 16.4)], aPL associated with CTDs [OR 3.1 (95% CI 1.5, 6.7)] and non-criteria APS [OR 5.9 (95% CI 1.7, 20.1)] compared with controls. Among clinical and laboratory criteria of APS, first trimester aCL IgG >40 UI/ml [OR 4.4 (95% CI 1.3, 14.4)], LA positivity [OR 6.5 (95% CI 1.3, 33.3)] and a history of pre-eclampsia at <34 weeks [OR 32.4 (95% CI 6.5, 161)] were the best independent first trimester predictors of severe MVM [area under the curve 0.74 (95% CI 0.6, 0.87)]. Conclusion Compared with healthy controls, pregnant subjects with aPL antibodies have an increased risk of placental lesions, suggesting MVM and FVM. First-trimester variables such as aCL IgG >40 UI/ml and a history of pre-eclampsia were significant predictors of both severe MVM and FVM.

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Serum Glutamate Is a Predictor for the Diagnosis of Multiple Sclerosis

The Scientific World JOURNAL ◽

10.1155/2017/9320802 ◽

2017 ◽

Vol 2017 ◽

pp. 1-5 ◽

Cited By ~ 7

Author(s):

Gheyath Al Gawwam ◽

Inas K. Sharquie

Keyword(s):

Multiple Sclerosis ◽

Area Under The Curve ◽

The Body ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Operating Characteristics ◽

Serum Samples ◽

Elisa Technique ◽

Autoimmune Demyelination ◽

Serum Glutamate

One neurotransmitter, glutamate, has been implicated in the autoimmune demyelination seen in multiple sclerosis (MS). Glutamate is present in many tissues in the body, so consideration should be given to whether the serum level of glutamate is likely well correlated with the activity of the disease. This research aimed to compare the serum glutamate levels from patients diagnosed with MS with those from an age-matched control population. A review of this data could shed light upon whether the serum testing of glutamate using Enzyme-Linked Immunosorbent Assay (ELISA) is a reliable indicator of MS activity. Serum samples were obtained from 55 patients with different patterns of MS and from 25 healthy adults as a control group. The ELISA technique was used to determine the glutamate levels in the serum samples. The mean serum glutamate level for patients with MS was1.318±0.543 nmol/ml and that of the controls was0.873±0.341 nmol/ml. The serum glutamate levels showed an area under the curve via the receiver operating characteristics (ROC) of 0.738, which was significant (pvalue = 0.001). The present study is the first to establish a strong connection between the serum glutamate levels and MS patients, where there was statistically significant elevation of serum glutamate in MS patients; hence this elevation might be used as a monitor to help in the diagnosis of MS patients.

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