Serum Epiplakin Might Be a Potential Serodiagnostic Biomarker for Bladder Cancer

Tumor markers that can be detected at an early stage are needed. Here, we evaluated the epiplakin expression levels in sera from patients with bladder cancer (BC). Using a micro-dot blot array, we evaluated epiplakin expression levels in 60 patients with BC, 20 patients with stone disease, and 28 healthy volunteers. The area under the curve (AUC) and best cut-off point were calculated using receiver-operating characteristic (ROC) analysis. Serum epiplakin levels were significantly higher in patients with BC than in those with stone disease (p = 0.0013) and in healthy volunteers (p < 0.0001). The AUC-ROC level for BC was 0.78 (95% confidence interval (CI) = 0.69–0.87). Using a cut-off point of 873, epiplakin expression levels exhibited 68.3% sensitivity and 79.2% specificity for BC. However, the serum epiplakin levels did not significantly differ by sex, age, pathological stage and grade, or urine cytology. We performed immunohistochemical staining using the same antibody on another cohort of 127 patients who underwent radical cystectomy. Univariate and multivariate analysis results showed no significant differences between epiplakin expression, clinicopathological findings, and patient prognoses. Our results showed that serum epiplakin might be a potential serodiagnostic biomarker in patients with BC.

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Expression Analysis of Circulating miR-22, miR-122, miR-217 and miR-367 as Promising Biomarkers of Acute Lymphoblastic Leukemia

10.21203/rs.3.rs-1097151/v1 ◽

2021 ◽

Author(s):

Fatemeh hosseinpour-soleimani ◽

Gholamreza Khamisipour ◽

Zahra Derakhshan ◽

Bahram Ahmadi

Keyword(s):

Acute Lymphoblastic Leukemia ◽

Roc Analysis ◽

Operating Characteristic ◽

Lymphoblastic Leukemia ◽

Area Under The Curve ◽

Diagnostic Value ◽

Healthy Individuals ◽

Quantitative Real Time Pcr ◽

Expression Levels

Abstract Background Currently, the role of serum-based biomarkers such as microRNAs in cancer diagnosis has been extensively established. This study aimed to determine expression levels of bioinformatically selected miRNAs and whether they can be used as biomarkers or a new therapeutic target in patients with Acute Lymphoblastic Leukemia (ALL). Materials and Methods The expression levels of serum miR-22, miR-122, miR-217, and miR-367 in 21 ALL patients and 21 healthy controls were measured using quantitative real-time PCR. The receiver operating characteristic (ROC) curve and the associated area under the curve (AUC) was used to assess candidate miRNAs' diagnostic value as a biomarker. Results The results showed that miR-217 was markedly decreased in patients with ALL compared to controls. Moreover, miR-22, miR-122, and miR-367 were found to be upregulated. Furthermore, ROC analysis showed that serum miR-217 and miR-367 could differentiate ALL patients from the healthy individuals, while miR-22 has approximate discriminatory power that requires further investigation. Conclusion Collectively, the results suggested that miR-217 may play a tumor suppressor role in ALL, whereas miR-22, miR-122, and miR-367 could function as an oncogene. Overall, miR-22, miR-217, and miR-367 could be considered possible biomarkers for the early diagnosis of ALL.

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The potential value of a pictorial atlas for aid in the visual diagnosis of 123I FP-CIT SPECT scans

Nuklearmedizin ◽

10.3413/nukmed-0230 ◽

2009 ◽

Vol 48 (04) ◽

pp. 173-178 ◽

Cited By ~ 3

Author(s):

H. Ham ◽

A. Dobbeleir ◽

P. Santens ◽

Y. D'Asseler ◽

I. Goethals

Keyword(s):

Diagnostic Accuracy ◽

Roc Analysis ◽

Operating Characteristic ◽

Interobserver Variability ◽

Area Under The Curve ◽

Visual Assessment ◽

Added Value ◽

Related Disorder ◽

Visual Diagnosis ◽

Spect Images

SummaryThe aim of our study was to evaluate the value of a pictorial atlas of 123I FP-CIT SPECT images for aid in the visual diagnosis. Patients, materials, methods: Sixty patients, of whom 20 were clinically diagnosed as ‘non-parkinsonian’ and 40 as having Parkinson's disease or any related disorder, were included in the study. An atlas consisting of 12 123I FP-CIT SPECT images was constructed first. Validity of the atlas was investigated by performing a receiver operating characteristic (ROC) analysis with the clinical diagnosis as the gold standard. The remaining 48 SPECT images were visually assessed twice by 5 observers, first with and secondly without consulting the atlas, or vice versa. The added value of the atlas was investigated by comparing the diagnostic accuracy and the interobserver variability for both methods. Results: ROC analysis performed on the atlas yielded an area under the curve of 1 for a threshold discriminating between clinically non-parkinsonian and parkinsonian patients that was situated between image 4 and 5 of the atlas. For the diagnostic accuracy, we found that the area under the ROC curve was systematically higher if observers had access to the atlas compared to when they had not (Wilcoxon's test, p<0.05). Also, the interobserver variability was significantly lower when observers used the atlas when compared to when they did not (p = 0.05). Conclusion: Diagnostic accuracy was significantly higher and interobserver variability significantly lower if observers had access to the atlas compared to when they had not. Hence, having a pictorial atlas available may facilitate the visual assessment of 123I FP-CIT SPECT scans.

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Discovery of Prognostic Markers for Early-Stage High-Grade Serous Ovarian Cancer by Maldi-Imaging

Cancers ◽

10.3390/cancers12082000 ◽

2020 ◽

Vol 12 (8) ◽

pp. 2000

Author(s):

Hagen Kulbe ◽

Oliver Klein ◽

Zhiyang Wu ◽

Eliane T. Taube ◽

Wanja Kassuhn ◽

...

Keyword(s):

Roc Analysis ◽

Operating Characteristic ◽

Prognostic Markers ◽

Early Stage ◽

Imaging Mass Spectrometry ◽

Maldi Imaging ◽

High Grade ◽

Proof Of Concept ◽

Tissue Sections ◽

Maldi Ims

With regard to relapse and survival, early-stage high-grade serous ovarian (HGSOC) patients comprise a heterogeneous group and there is no clear consensus on first-line treatment. Currently, no prognostic markers are available for risk assessment by standard targeted immunohistochemistry and novel approaches are urgently required. Here, we applied MALDI-imaging mass spectrometry (MALDI-IMS), a new method to identify distinct mass profiles including protein signatures on paraffin-embedded tissue sections. In search of prognostic biomarker candidates, we compared proteomic profiles of primary tumor sections from early-stage HGSOC patients with either recurrent (RD) or non-recurrent disease (N = 4; each group) as a proof of concept study. In total, MALDI-IMS analysis resulted in 7537 spectra from the malignant tumor areas. Using receiver operating characteristic (ROC) analysis, 151 peptides were able to discriminate between patients with RD and non-RD (AUC > 0.6 or < 0.4; p < 0.01), and 13 of them could be annotated to proteins. Strongest expression levels of specific peptides linked to Keratin type1 and Collagen alpha-2(I) were observed and associated with poor prognosis (AUC > 0.7). These results confirm that in using IMS, we could identify new candidates to predict clinical outcome and treatment extent for patients with early-stage HGSOC.

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Immunoproteomics approach revealed elevated autoantibody levels against ANXA1 in early stage gallbladder carcinoma

BMC Cancer ◽

10.1186/s12885-020-07676-6 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Javed Akhtar ◽

Ratna Priya ◽

Vaishali Jain ◽

Puja Sakhuja ◽

Anil Kumar Agarwal ◽

...

Keyword(s):

Healthy Volunteers ◽

Gallbladder Carcinoma ◽

Early Stage ◽

Mass Spectrometric ◽

Mass Spectrometric Analysis ◽

Spectrometric Analysis ◽

Stage Iiia ◽

Expression Levels ◽

Tandem Mass Spectrometric ◽

Pdquest Software

Abstract Background Early diagnosis is important for the timely treatment of gallbladder carcinoma (GBC) patients and may lead to increased survival outcomes. Here, we have applied serological proteome analysis (SERPA), an immunoproteomics approach, for the detection of ‘tumor-associated antigens (TAAs) that elicit humoral response’ in early stage GBC patients. Methods Total protein from pooled tumor tissue of GBC patients (n = 7) was resolved by two-dimensional gel electrophoresis (2-DE) followed by immunoblotting using pooled blood plasma from healthy volunteers (n = 11) or gallstone disease (GSD) cases (n = 11) or early stage GBC (Stage I and II) (n = 5) or GBC stage IIIA (n = 9). 2-D gel and immunoblot images were acquired and analyzed using PDQuest software to identify immunoreactive spots in GBC cases in comparison to controls. Proteins from immunoreactive spots were identified by liquid chromatography- tandem mass spectrometric analysis (LC-MS/MS). Autoantibody levels for two of the functionally relevant proteins were investigated in individual plasma samples (52 cases and 89 controls) by dot blot assay using recombinant proteins. Results Image analysis using PDQuest software identified 25 protein spots with significantly high or specific immunoreactivity in GBC cases. Mass spectrometric analysis of 8 corresponding protein spots showing intense immunoreactivity (based on densitometric analysis) in early stage GBC or GBC stage IIIA cases led to the identification of 27 proteins. Some of the identified proteins include ANXA1, HSPD1, CA1, CA2, ALDOA and CTSD. Among the two proteins, namely ANXA1 and HSPD1 verified using a cohort of samples, significantly elevated autoantibody levels against ANXA1 were observed in early stage GBC cases in comparison to healthy volunteers or GSD cases (unpaired t-test, p < 0.05). Receiver operating characteristic (ROC) curve analysis for ANXA1 showed an Area under the Curve (AUC) of 0.69, with 41.7% sensitivity against a specificity of 89.9% for early stage GBC. IHC analysis for ANXA1 protein showed ‘high’ expression levels in 72% of GBC cases whereas all the controls showed ‘low’ expression levels. Conclusions The study suggests that the ANXA1 autoantibody levels against ANXA1 may be potentially employed for early stage detection of GBC patients. Other proteins could also be explored and verified in a large cohort of clinical samples.

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CA549 and TPS Patterns in the Diagnosis and Staging of Patients with Breast Carcinoma

The International Journal of Biological Markers ◽

10.1177/172460089601100403 ◽

1996 ◽

Vol 11 (4) ◽

pp. 198-202 ◽

Cited By ~ 2

Author(s):

H.G. Vibert ◽

A.S. Houston ◽

G.P. Wilkins ◽

P.M. Kemp ◽

M.A. Macleod

Keyword(s):

Roc Analysis ◽

Operating Characteristic ◽

Benign Breast Disease ◽

Area Under The Curve ◽

Breast Disease ◽

Clinical Value ◽

Variable Threshold ◽

Individual Marker ◽

The Difference ◽

Active Disease

This study compares the clinical value of the breast cancer tumour markers CA549 and TPS, and their tandem use when one or both markers indicate abnormality. For 144 patients presenting with active disease, 33 were classified as Stage I, 37 as Stage II, 40 as Stage III and 34 as Stage TV. For these patients the sensitivity of CA549 using a cut-off of 10 U/ml was 27%, 32%, 42% and 79%, respectively. The sensitivity of TPS for each stage using a cut-off of 100 U/l was 12%, 22%, 28% and 73%, respectively. At these cut-off levels, 36%, 46%, 63% and 91% of patients, respectively, have either CA549 or TPS or both markers raised. For 161 patients with diagnosed benign breast disease, the specificity of marker levels was 96% for CA549, 88% for TPS and 84% for tandem use. CA549 is shown to be superior to TPS and this was confirmed by Receiver Operating Characteristic (ROC) analysis using variable threshold levels, with the areas under the curves for all stages combined being 0.74 ± 0.03 (1SD) and 0.66 ± 0.03, respectively. The corresponding area under the curve for tandem use (0.75 ± 0.03) is marginally greater than for either individual marker, although the difference with respect to CA549 is statistically insignificant.

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Study On Coronary Dissection Complication Caused by Uneven Rotational Atherectomy Due To Guidewire Bias for Severe Calcified Lesions

10.21203/rs.3.rs-999355/v1 ◽

2021 ◽

Author(s):

Fei Ye ◽

Wei You ◽

Hong-li Zhang ◽

Tian Xu ◽

Pei-na Meng ◽

...

Keyword(s):

Roc Analysis ◽

Operating Characteristic ◽

Area Under The Curve ◽

Coronary Calcification ◽

Rotational Atherectomy ◽

Cross Sectional ◽

Actual Meaning ◽

Oct Imaging ◽

Calcified Coronary Lesions ◽

Catheter Location

Abstract BACKGROUND In the treatment of coronary calcification by rotational atherectomy (ROTA), guidewire bias is often considered to lead to procedure associated coronary dissections or perforations. However, the actual meaning of guidewire bias is unclear, though it usually refers to the cross-section location of the intravascular imaging (IVI) catheter in the coronary artery. OBJECTIVES This study tentatively explores the quantitative criteria in optical coherence tomography (OCT) imaging of guidewire bias which may cause ROTA induced coronary dissection. METHODS A total of twenty-one patients with severe calcified coronary lesions who has undergone ROTA treatment were enrolled in our study. These patients were detected by OCT successfully pre- and post-ROTA. All the observational coronary segments were analyzed cross-sectionally at every mm interval after manual coregistration of OCT imaging pre- and post-ROTA. ROTA related coronary dissection was the primary endpoint. RESULTS A total of 388 OCT cross-sectional images were effectively measured and analyzed for distribution and characteristics of plaque and OCT catheter location pre-ROTA, and the presence or absence of coronary dissections post-ROTA after manual coregistration. According to the receiver operating characteristic (ROC) analysis, distance from the center of OCT catheter to media at the bias direction (Dcmb) (area under the curve (AUC): 1.000, p<0.001, 95% confidence intervals (CI): 0.999 to 1.000) and touch angle (AUC: 0.988, p<0.001, 95%CI: 0.968 to 1.000) had a higher correlation with ROTA-related coronary dissection with the corresponding cutoff value of 0.720mm and 98.2º significantly. CONCLUSIONS Dcmb and touch angle detected by OCT are two very valuable and convenient independent predictors of ROTA-related coronary intimal dissections caused by guidewire bias.

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Early Prediction of Malignant Cerebellar Edema in Posterior Circulation Stroke Using Quantitative Lesion Water Uptake

Neurosurgery ◽

10.1093/neuros/nyaa438 ◽

2020 ◽

Author(s):

Gabriel Broocks ◽

Sarah Elsayed ◽

Helge Kniep ◽

Andre Kemmling ◽

Fabian Flottmann ◽

...

Keyword(s):

Water Uptake ◽

Roc Analysis ◽

Early Stage ◽

Area Under The Curve ◽

Posterior Circulation ◽

Receiver Operating Curve ◽

Imaging Biomarker ◽

Anterior Circulation ◽

Ischemic Lesion ◽

Posterior Circulation Stroke

Abstract BACKGROUND Malignant cerebellar edema (MCE) is a life-threatening complication of ischemic posterior circulation stroke that requires timely diagnosis and management. Yet, there is no established imaging biomarker that may serve as predictor of MCE. Early edematous water uptake can be determined using quantitative lesion water uptake, but this biomarker has only been applied in anterior circulation strokes. OBJECTIVE To test the hypothesis that lesion water uptake in early posterior circulation stroke predicts MCE. METHODS A total 179 patients with posterior circulation stroke and multimodal admission CT were included. A total of 35 (19.5%) patients developed MCE defined by using an established 10-point scale in follow-up CT, of which ≥4 points are considered malignant. Posterior circulation net water uptake (pcNWU) was quantified in admission CT based on CT densitometry and compared with posterior circulation Acute Stroke Prognosis Early CT Score (pc-ASPECTS) as predictor of MCE using receiver operating curve (ROC) analysis and logistic regression analysis. RESULTS Acute pcNWU within the early ischemic lesion was 24.6% (±8.4) for malignant and 7.2% (±7.4) for nonmalignant infarctions, respectively (P < .0001). Based on ROC analysis, pcNWU above 14.9% identified MCE with high discriminative power (area under the curve: 0.94; 95% CI: 0.89-0.97). Early pcNWU (odds ratio [OR]: 1.28; 95% CI: 1.15-1.42, P < .0001) and pc-ASPECTS (OR: 0.71, 95% CI: 0.53-0.95, P = .02) were associated with MCE, adjusted for age and recanalization status. CONCLUSION Quantitative pcNWU in early posterior circulation stroke is an important marker for MCE. Besides pc-ASPECTS, lesion water uptake measurements may further support identifying patients at risk for MCE at an early stage indicating stricter monitoring and consideration for further therapeutic measures.

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Pathfast Presepsin Assay for Early Diagnosis of Systemic Inflammatory Response Syndrome in Patients with Nephrolithiasis

BioMed Research International ◽

10.1155/2015/792572 ◽

2015 ◽

Vol 2015 ◽

pp. 1-6 ◽

Cited By ~ 1

Author(s):

Yan-song Hou ◽

Hua Wang ◽

Hao Chen ◽

Ling-feng Wu ◽

Lin-feng Lu ◽

...

Keyword(s):

Roc Analysis ◽

Operating Characteristic ◽

Diagnostic Marker ◽

Early Stage ◽

Diagnostic Value ◽

Bacterial Sepsis ◽

Diagnostic Ability ◽

Highly Sensitive ◽

Comparable Performance ◽

Median Plasma

It is relatively difficult to diagnose bacterial sepsis in nephrolithiasis patients. The aim of the study is to evaluate the diagnostic ability of presepsin in the differential diagnosis including SIRS, infection, or sepsis and to compare its diagnostic value with other markers, mainly as CRP, procalcitonin (PCT), and white blood cell (WBC) in patients of nephrolithiasis presenting with SIRS. 39 patients of nephrolithiasis who were diagnosed as SIRS were prospectively investigated. Plasma presepsin was detected by Pathfast presepsin assay system; CRP and PCT were measured as well. Additionally, 25 nephrolithiasis patients without SIRS were included. At all timing samples, patients were classified as SIRS or non-SIRS group. Median plasma presepsin levels were significantly increased in the SIRS group compared with non-SIRS group (452 pg/mL versus 178 ng/mL,P<0.001), and presepsin was markedly elevated even in the early stage of SIRS (584 pg/mL 6 h, 660 pg/mL 24 h versus 452 pg/mL,P<0.001). According to the receiver-operating characteristic (ROC) analysis, presepsin demonstrated a high diagnostic value compared with either PCT or CRP. In the early stage of SIRS, presepsin remained a highly sensitive (74.7%) and specific (88.4%) diagnostic marker compared with either PCT, CRP, or WBC. Moreover, the areas under the curve (AUCs) of presepsin (84.6%) were also superior to those seen in either PCT (79.6%) or CRP (71.8%). Thus plasma presepsin levels have comparable performance in SIRS for patients with nephrolithiasis.

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Serum Indoleamine 2,3-Dioxygenase Activity Predicts Prognosis of Pulmonary Tuberculosis

Clinical and Vaccine Immunology ◽

10.1128/cvi.05402-11 ◽

2012 ◽

Vol 19 (3) ◽

pp. 436-442 ◽

Cited By ~ 55

Author(s):

Yuzo Suzuki ◽

Takafumi Suda ◽

Kazuhiro Asada ◽

Seiichi Miwa ◽

Masako Suzuki ◽

...

Keyword(s):

Poor Prognosis ◽

Roc Analysis ◽

Operating Characteristic ◽

Area Under The Curve ◽

Major Health Problem ◽

Major Health ◽

Indoleamine 2,3 Dioxygenase ◽

Rate Limiting Step ◽

Limiting Step ◽

Rate Limiting

ABSTRACTTuberculosis (TB) continues to be a major health problem, and there are few biomarkers for predicting prognosis. Indoleamine 2,3-dioxygenase (IDO), a potent immunoregulatory molecule, catalyzes the rate-limiting step of tryptophan (Trp) degradation in the kynurenine (Kyn) pathway. An increase in IDO activity determined by the serum Trp/Kyn ratio has been shown to be associated with poor prognosis in cancers and bacteremia. In TB, however, there are no studies measuring serum IDO activity to determine its clinical significance. We evaluated serum IDO activity with 174 pulmonary TB (PTB) patients and 85 controls, using liquid chromatography/electrospray ionization tandem mass spectrometry. IDO activity was estimated by calculating the serum Kyn-to-Trp ratio. PTB patients had significantly higher Kyn concentrations and IDO activity and significantly lower Trp concentrations (P< 0.0001,P< 0.0001, andP< 0.0001, respectively) than the controls. Of 174 PTB patients, 39 (22.4%) died. The patients who died had significantly higher concentrations of Kyn and significantly lower Trp concentrations, resulting in significantly higher IDO activity (P< 0.0001,P< 0.0001, andP< 0.0001, respectively). In a receiver operating characteristic (ROC) analysis, serum IDO activity had the highest area under the curve (0.850), and this activity was an independent prognostic factor in multivariate analysis. These results suggest that serum IDO activity can be used as a novel prognostic marker in PTB.

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Evaluation of serum AFP and DCP levels in the diagnosis of early-stage HBV-related HCC under different backgrounds

Journal of International Medical Research ◽

10.1177/0300060520969087 ◽

2020 ◽

Vol 48 (10) ◽

pp. 030006052096908

Author(s):

Ting Song ◽

Lili Wang ◽

Ruopei Xin ◽

Liping Zhang ◽

Yun Tian

Keyword(s):

Roc Curve ◽

Diagnostic Performance ◽

Operating Characteristic ◽

Early Stage ◽

Area Under The Curve ◽

Curve Analysis ◽

Roc Curve Analysis ◽

Chronic Hbv Infection ◽

B Virus ◽

Chronic Hbv

Objective This study compared the diagnostic performance of alpha-fetoprotein (AFP) and des-gamma-carboxyprothrombin (DCP) in early-stage hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) under different backgrounds. Methods Patients were enrolled and divided in four groups: chronic HBV infection (CHB), liver cirrhosis (LC), early-stage CHB-HCC, and early-stage LC-HCC. Serum AFP and DCP levels were measured. Receiver-operating characteristic (ROC) curve and area under the curve (AUC) analyses were applied to compare the diagnostic performance of DCP and AFP for HCC. Results In total, 200 patients were enrolled, including 48, 64, 33, and 55 patients with CHB, LC, CHB-HCC, and LC-HCC, respectively. ROC curve analysis revealed that the AUCs of AFP, DCP, and their combination in differentiating early-stage LC-HCC from LC were 0.776, 0.758, and 0.786, respectively. The values of these markers in discriminating early-stage CHB-HCC from CHB were 0.828, 0.731, and 0.862, respectively. Conclusions DCP was inferior to AFP in differentiating early-stage CHB-HCC from CHB. However, AFP and DCP displayed similar performance in distinguishing early-stage LC-HCC and LC.

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