Relation between GSTP1 polymorphism and oxidative stress in patients with hepatocellular carcinoma

Abstract Background Glutathione can reduce the oxidative stress by converting the unstable to stable molecules and its status in hepatocellular carcinoma (HCC) is correlated with tumor growth and metastasis. Glutathione S-transferase Pi (GSTP1) is reported to detoxify the xenobiotic substrates by catalyzing their conjugation to reduced glutathione (GSH) and its over-expression was demonstrated in the early stages of HCC, while loss of GSTP1 has been suggested to increase the risk of deoxyribonucleic acid (DNA) damage and mutation. The aim of this study is to assess the relationship of GSTP1 polymorphism Ile105Val (rs1695 A > G) with HCC risk, and to investigate the oxidative stress status of HCC patients by measuring the antioxidant glutathione (GSH) levels. This study was conducted on 99 newly diagnosed HCC patients and 80 apparently healthy individuals as a normal control group. All participants were subjected to the measurement of plasma GSH levels according to Ellman’s method, and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for the detection of GSTP1 polymorphismIle105Val (rs1695 A > G). Results The occurrence of either the mutant homozygous or the mutant heterozygous genotype of GSTP1 was significantly higher in HCC patients, while the occurrence of the wild genotype was significantly higher among the normal control subjects. Mutant GSTP1 genotype, older age, male gender, and high serum alanine aminotransferase (ALT) were associated with increased risk of development of HCC. The best sensitivity, specificity, PPV (positive predictive value), NPV (negative predictive value), and overall diagnostic performance for plasma GSH at a cutoff level of 2003.5 μM/mg were 57.6%, 52.5%, 60%, and 40%. The area under the curve for GSH was 0.562. Conclusion Mutant GSTP1 genotype was an independent prognostic factor for increased HCC risk which can be used in a risk assessment model for HCC. Plasma GSH presents insufficient sensitivity and specificity for HCC.

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Establishment and Characterization of an Empirical Biomarker SS/PV-ROC Plot Using Results of the UBC® Rapid Test in Bladder Cancer

Entropy ◽

10.3390/e22070729 ◽

2020 ◽

Vol 22 (7) ◽

pp. 729 ◽

Cited By ~ 1

Author(s):

Peter Oehr ◽

Thorsten Ecke

Keyword(s):

Bladder Cancer ◽

Roc Curve ◽

Predictive Value ◽

Area Under The Curve ◽

Rapid Test ◽

Roc Curves ◽

Threshold Value ◽

Control Group ◽

Predictive Values ◽

Sensitivity Specificity

Background: This investigation included both a study of potential non-invasive diagnostic approaches for the bladder cancer biomarker UBC® Rapid Test and a study including comparative methods about sensitivity–specificity characteristic (SS-ROC) and predictive receiver operating characteristic (PV-ROC) curves that used bladder cancer as a useful example. Methods: The study included 289 urine samples from patients with tumors of the urinary bladder, patients with non-evidence of disease (NED) and healthy controls. The UBC® Rapid Test is a qualitative point of care assay. Using a photometric reader, quantitative data can also be obtained. Data for pairs of sensitivity/specificity as well as positive/negative predictive values were created by variation of threshold values for the whole patient cohort, as well as for the tumor-free control group. Based on these data, sensitivity–specificity and predictive value threshold distribution curves were constructed and transformed into SS-ROC and PV-ROC curves, which were included in a single SS/PV-ROC plot. Results: The curves revealed TPP-asymmetric improper curves which cross the diagonal from above. Evaluation of the PV-ROC curve showed that two or more distinct positive predictive values (PPV) can correspond to the same value of a negative predictive value (NPV) and vice versa, indicating a complexity in PV-ROC curves which did not exist in SS-ROC curves. In contrast to the SS-ROC curve, the PV-ROC curve had neither an area under the curve (AUC) nor a range from 0% to 100%. Sensitivity of the qualitative assay was 58.5% and specificity 88.2%, PPV was 75.6% and NPV 77.3%, at a threshold value of approximately 12.5 µg/L. Conclusions: The SS/PV-ROC plot is a new diagnostic approach which can be used for direct judgement of gain and loss of predictive values, sensitivity and specificity according to varied threshold value changes, enabling characterization, comparison and evaluation of qualitative and quantitative bioassays.

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Circulating tumour DNA methylation in hepatocellular carcinoma diagnosis using digital droplet PCR

Journal of International Medical Research ◽

10.1177/0300060521992962 ◽

2021 ◽

Vol 49 (3) ◽

pp. 030006052199296

Author(s):

Juan Wang ◽

Liu Yang ◽

Yanjun Diao ◽

Jiayun Liu ◽

Jinjie Li ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Dna Methylation ◽

Likelihood Ratio ◽

Predictive Value ◽

Positive Likelihood Ratio ◽

Negative Likelihood Ratio ◽

Control Group ◽

Control Subjects ◽

Droplet Pcr ◽

Healthy Control

Objective To evaluate the performance of a DNA methylation-based digital droplet polymerase chain reaction (ddPCR) assay to detect aberrant DNA methylation in cell-free DNA (cfDNA) and to determine its application in the detection of hepatocellular carcinoma (HCC). Methods The present study recruited patients with liver-related diseases and healthy control subjects. Blood samples were used for the extraction of cfDNA, which was then bisulfite converted and the extent of DNA methylation quantified using a ddPCR platform. Results A total of 97 patients with HCC, 80 healthy control subjects and 46 patients with chronic hepatitis B/C virus infection were enrolled in the study. The level of cfDNA in the HCC group was significantly higher than that in the healthy control group. For the detection of HCC, based on a cut-off value of 15.7% for the cfDNA methylation ratio, the sensitivity and specificity were 78.57% and 89.38%, respectively. The diagnostic accuracy was 85.27%, the positive predictive value was 81.91% and the negative predictive value was 87.20%. The positive likelihood ratio of 15.7% in HCC diagnosis was 7.40, while the negative likelihood ratio was 0.24. Conclusions A sensitive methylation-based assay might serve as a liquid biopsy test for diagnosing HCC.

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Evaluation of alpha-l-fucosidase for the diagnosis of hepatocellular carcinoma based on meta-analysis

LaboratoriumsMedizin ◽

10.1515/labmed-2019-0152 ◽

2020 ◽

Vol 0 (0) ◽

Cited By ~ 1

Author(s):

Lei Xi ◽

Chunqing Yang

Keyword(s):

Hepatocellular Carcinoma ◽

Operating Characteristic ◽

Meta Analysis ◽

Area Under The Curve ◽

Diagnostic Odds Ratio ◽

Diagnostic Value ◽

Receiver Operating Characteristic Curves ◽

Sensitivity Specificity ◽

Review Manager

AbstractObjectivesThe main aim of the present study was to assess the diagnostic value of alpha-l-fucosidase (AFU) for hepatocellular carcinoma (HCC).MethodsStudies that explored the diagnostic value of AFU in HCC were searched in EMBASE, SCI, and PUBMED. The sensitivity, specificity, and DOR about the accuracy of serum AFU in the diagnosis of HCC were pooled. The methodological quality of each article was evaluated with QUADAS-2 (quality assessment for studies of diagnostic accuracy 2). Receiver operating characteristic curves (ROC) analysis was performed. Statistical analysis was conducted by using Review Manager 5 and Open Meta-analyst.ResultsEighteen studies were selected in this study. The pooled estimates for AFU vs. α-fetoprotein (AFP) in the diagnosis of HCC in 18 studies were as follows: sensitivity of 0.7352 (0.6827, 0.7818) vs. 0.7501 (0.6725, 0.8144), and specificity of 0.7681 (0.6946, 0.8283) vs. 0.8208 (0.7586, 0.8697), diagnostic odds ratio (DOR) of 7.974(5.302, 11.993) vs. 13.401 (8.359, 21.483), area under the curve (AUC) of 0.7968 vs. 0.8451, respectively.ConclusionsAFU is comparable to AFP for the diagnosis of HCC.

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New screening approach to detecting congenital syphilis in China: a retrospective cohort study

Archives of Disease in Childhood ◽

10.1136/archdischild-2020-320549 ◽

2020 ◽

pp. archdischild-2020-320549

Author(s):

Fang Hu ◽

Shuai-Jun Guo ◽

Jian-Jun Lu ◽

Ning-Xuan Hua ◽

Yan-Yan Song ◽

...

Keyword(s):

Predictive Value ◽

Congenital Syphilis ◽

Area Under The Curve ◽

Diagnostic Tools ◽

Operating Characteristics ◽

Loss To Follow Up ◽

Sensitivity Specificity ◽

Mother To Child ◽

Rule Out

BackgroundDiagnosis of congenital syphilis (CS) is not straightforward and can be challenging. This study aimed to evaluate the validity of an algorithm using timing of maternal antisyphilis treatment and titres of non-treponemal antibody as predictors of CS.MethodsConfirmed CS cases and those where CS was excluded were obtained from the Guangzhou Prevention of Mother-to-Child Transmission of syphilis programme between 2011 and 2019. We calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) using receiver operating characteristics (ROC) in two situations: (1) receiving antisyphilis treatment or no-treatment during pregnancy and (2) initiating treatment before 28 gestational weeks (GWs), initiating after 28 GWs or receiving no treatment for syphilis seropositive women.ResultsAmong 1558 syphilis-exposed children, 39 had confirmed CS. Area under the curve, sensitivity and specificity of maternal non-treponemal titres before treatment and treatment during pregnancy were 0.80, 76.9%, 78.7% and 0.79, 69.2%, 88.7%, respectively, for children with CS. For the algorithm, ROC results showed that PPV and NPV for predicting CS were 37.3% and 96.4% (non-treponemal titres cut-off value 1:8 and no antisyphilis treatment), 9.4% and 100% (non-treponemal titres cut-off value 1:16 and treatment after 28 GWs), 4.2% and 99.5% (non-treponemal titres cut-off value 1:32 and treatment before 28 GWs), respectively.ConclusionsAn algorithm using maternal non-treponemal titres and timing of treatment during pregnancy could be an effective strategy to diagnose or rule out CS, especially when the rate of loss to follow-up is high or there are no straightforward diagnostic tools.

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Validation of the SavvyCheckTM Vaginal Yeast Test for Screening Pregnant Women for Vulvovaginal Candidosis: A Prospective, Cross-Sectional Study

Journal of Fungi ◽

10.3390/jof7030233 ◽

2021 ◽

Vol 7 (3) ◽

pp. 233

Author(s):

Philipp Foessleitner ◽

Herbert Kiss ◽

Julia Deinsberger ◽

Julia Ott ◽

Lorenz Zierhut ◽

...

Keyword(s):

Pregnant Women ◽

Predictive Value ◽

Point Of Care ◽

Cross Sectional Study ◽

Control Group ◽

Gram Stain ◽

Cross Sectional ◽

Point Of Care Test ◽

Increased Risk ◽

Vulvovaginal Candidosis

Pregnant women have an increased risk of vulvovaginal candidosis. Recurrent candidosis is under debate as a contributor to preterm birth, and vertical transmission may cause diaper dermatitis and oral thrush in the newborn. Apart from cultural methods, the gold standard for diagnosing candidosis is Gram staining, which is time-consuming and requires laboratory facilities. The objective of this prospective study was to validate a point-of-care vaginal yeast detection assay (SavvyCheckÔ Vaginal Yeast Test) and to evaluate it in asymptomatic pregnant women. We enrolled 200 participants, 100 of whom had vulvovaginal candidosis according to Gram stain (study group) and 100 were healthy pregnant controls (control group). Of these, 22 participants (11%) had invalid test results. The point-of-care test of the remaining 85 and 93 study participants in the study and control groups, respectively, showed a sensitivity of 94.1%, specificity of 98.9%, positive predictive value of 90.3%, and negative predictive value of 99.4% when compared with Gram stain. In conclusion, we found a high correlation between the SavvyCheckÔ Vaginal Yeast Test and Gram-stained smears during pregnancy. This suggests a potential role of this point-of-care test as a screening tool for asymptomatic pregnant women in early gestation.

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Diagnostic Value of Vaginal Microecology, Serum miR-18a, and PD-L1 for Identifying HPV-Positive Cervical Cancer

Technology in Cancer Research & Treatment ◽

10.1177/1533033821995281 ◽

2021 ◽

Vol 20 ◽

pp. 153303382199528

Author(s):

Yumei Zhang ◽

Sujuan Qiu ◽

Yueli Guo ◽

Jiaqin Zhang ◽

Xiaoqing Wu ◽

...

Keyword(s):

Cervical Cancer ◽

Area Under The Curve ◽

Serum Levels ◽

Diagnostic Value ◽

High Serum ◽

Control Group ◽

Observation Group ◽

Positive Group ◽

Microbial Dysbiosis ◽

Programmed Death

Objective: We aimed to investigate the diagnostic value of the vaginal microecology, serum miR-18a, and programmed death ligand-1 (PD-L1) for human papillomavirus (HPV)-positive cervical cancer. Methods: Eighty-four patients with HPV-positive cervical cancer were assigned to the observation group, 107 HPV-positive patients without cervical cancer were assigned to the positive group, and 191 healthy women were assigned to the control group. Vaginal microecology and serum levels of miR-18a and PD-L1 on the surface of CD4+ and CD8+ T cells were compared among the 3 groups. The observation group was further divided into subgroups according to patients’ characteristics for comparison. The diagnostic value of miR-18a and PD-L1 for HPV-positive cervical cancer was investigated. Results: Women in the control group had better vaginal microecology and lower levels of miR-18a and PD-L1 than those in the observation and the positive groups (all P < 0.05). Compared with the positive group, the observation group had similar vaginal microecology (all P > 0.05) but higher levels of miR-18a and PD-L1 (all P < 0.05). Moreover, the patients at stage III had higher levels of miR-18a and PD-L1 than those at stage I and II (all P < 0.05). The values of area under the curve for miR-18a and PD-L1 in the diagnosis of HPV-positive cervical cancer were over 0.8 (all P < 0.001). Conclusion: Patients with HPV-positive cervical cancer have vaginal microbial dysbiosis and high serum levels of miR-18a and PD-L1. miR-18a and PD-L1 have diagnostic value for identifying HPV-positive cervical cancer.

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Value and Diagnostic Efficacy of Fetal Morphology Assessment Using Ultrasound in A Poor-Resource Setting

Diagnostics ◽

10.3390/diagnostics9030109 ◽

2019 ◽

Vol 9 (3) ◽

pp. 109 ◽

Cited By ~ 1

Author(s):

Ukweh ◽

Ugbem ◽

Okeke ◽

Ekpo

Keyword(s):

Predictive Value ◽

Performance Metrics ◽

Area Under The Curve ◽

Youden Index ◽

Likelihood Ratios ◽

Diagnostic Efficacy ◽

Predictive Values ◽

Resource Setting ◽

Post Test ◽

Sensitivity Specificity

Background: Ultrasound is operator-dependent, and its value and efficacy in fetal morphology assessment in a low-resource setting is poorly understood. We assessed the value and efficacy of fetal morphology ultrasound assessment in a Nigerian setting. Materials and Methods: We surveyed fetal morphology ultrasound performed across five facilities and followed-up each fetus to ascertain the outcome. Fetuses were surveyed in the second trimester (18th–22nd weeks) using the International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) guideline. Clinical and surgical reports were used as references to assess the diagnostic efficacy of ultrasound in livebirths, and autopsy reports to confirm anomalies in terminated pregnancies, spontaneous abortions, intrauterine fetal deaths, and still births. We calculated sensitivity, specificity, positive and negative predictive values, Area under the curve (AUC), Youden index, likelihood ratios, and post-test probabilities. Results: In total, 6520 fetuses of women aged 15–46 years (mean = 31.7 years) were surveyed. The overall sensitivity, specificity, and AUC were 77.1 (95% CI: 68–84.6), 99.5 (95% CI: 99.3–99.7), and 88.3 (95% CI: 83.7–92.2), respectively. Other performance metrics were: positive predictive value, 72.4 (95% CI: 64.7–79.0), negative predictive value, 99.6 (95% CI: 99.5–99.7), and Youden index (77.1%). Abnormality prevalence was 1.67% (95% CI: 1.37–2.01), and the positive and negative likelihood ratios were 254 (95% CI: 107.7–221.4) and 0.23 (95% CI: 0.16–0.33), respectively. The post-test probability for positive test was 72% (95% CI: 65–79). Conclusion: Fetal morphology assessment is valuable in a poor economics setting, however, the variation in the diagnostic efficacy across facilities and the limitations associated with the detection of circulatory system anomalies need to be addressed.

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Identification of the most specific markers to differentiate primary pulmonary carcinoma from metastatic gastrointestinal carcinoma to the lung

Diagnostic Pathology ◽

10.1186/s13000-021-01184-2 ◽

2022 ◽

Vol 17 (1) ◽

Author(s):

Bachar Alabdullah ◽

Amir Hadji-Ashrafy

Keyword(s):

Gastrointestinal Tract ◽

Predictive Value ◽

Regression Models ◽

Area Under The Curve ◽

Roc Curves ◽

Multivariate Models ◽

Gastrointestinal Carcinoma ◽

Lung Tumours ◽

Napsin A ◽

Sensitivity Specificity

Abstract Background A number of biomarkers have the potential of differentiating between primary lung tumours and secondary lung tumours from the gastrointestinal tract, however, a standardised panel for that purpose does not exist yet. We aimed to identify the smallest panel that is most sensitive and specific at differentiating between primary lung tumours and secondary lung tumours from the gastrointestinal tract. Methods A total of 170 samples were collected, including 140 primary and 30 non-primary lung tumours and staining for CK7, Napsin-A, TTF1, CK20, CDX2, and SATB2 was performed via tissue microarray. The data was then analysed using univariate regression models and a combination of multivariate regression models and Receiver Operating Characteristic (ROC) curves. Results Univariate regression models confirmed the 6 biomarkers’ ability to independently predict the primary outcome (p < 0.001). Multivariate models of 2-biomarker combinations identified 11 combinations with statistically significant odds ratios (ORs) (p < 0.05), of which TTF1/CDX2 had the highest area under the curve (AUC) (0.983, 0.960–1.000 95% CI). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 75.7, 100, 100, and 37.5% respectively. Multivariate models of 3-biomarker combinations identified 4 combinations with statistically significant ORs (p < 0.05), of which CK7/CK20/SATB2 had the highest AUC (0.965, 0.930–1.000 95% CI). The sensitivity, specificity, PPV, and NPV were 85.1, 100, 100, and 41.7% respectively. Multivariate models of 4-biomarker combinations did not identify any combinations with statistically significant ORs (p < 0.05). Conclusions The analysis identified the combination of CK7/CK20/SATB2 to be the smallest panel with the highest sensitivity (85.1%) and specificity (100%) for predicting tumour origin with an ROC AUC of 0.965 (p < 0.001; SE: 0.018, 0.930–1.000 95% CI).

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PEMERIKSAAN TINGKAT sdLDL SERUM SEBAGAI PETANDA DIAGNOSTIK STENOSIS KORONER (Serum sdLDL Level as A Diagnostic Marker of Coronary Stenosis)

INDONESIAN JOURNAL OF CLINICAL PATHOLOGY AND MEDICAL LABORATORY ◽

10.24293/ijcpml.v22i1.1215 ◽

2018 ◽

Vol 22 (1) ◽

pp. 9

Author(s):

Indranila K Samsuria ◽

Laily Adninta

Keyword(s):

Predictive Value ◽

Coronary Stenosis ◽

Area Under The Curve ◽

Clinical Pathology ◽

Diagnostic Value ◽

T Test ◽

Cross Sectional ◽

Increased Risk ◽

Test Kit ◽

Vascular Stenosis

Small dense LDL (sdLDL) is the LDL which particles are small and dense, it is pro-atherogenic. Increased levels of serum sdLDL areassociated with an increased risk of coronary stenosis. The aim of this study was to examine the diagnostic value of sd LDL in coronarystenosis. An analytical observational study with cross sectional approach was conducted at the Department of Clinical Pathology, MedicalFaculty of Diponegoro University/Dr. Kariadi Hospital and the Unit of Cardiac diseases during the period of March-October 2013. Thesubjects were 39 patients suspected of suffering a coronary stenosis. The diagnosis of coronary stenosis, degree of stenosis and numberof vascular stenosis was established at the time of cardiac catheterization. SdLDL assessment used a test kit. The statistical analysis usedwere unpaired t-test, Spearman correlation test, ROC analysis and diagnostic test. LDL levels in stenosis subjects, 35.4±9.01 mg/dL weresignificantly higher compared to levels in subjects that had no stenosis, 20.7±7.10 mg/dL (p<0.001; unpaired t-test). Correlation testresults showed a correlation between levels of serum sdLDL with severe degree of stenosis (correlation coefficient -0.64, p <0.001) and amoderate positive correlation between the number of vascular stenosis (Coefficient correlation 0.46; p=0.003; Spearman Correlation’sTest). The area under the curve of ROC was 0.9 (p <0.001). The cut off levels sdLDL were used to detect stenosis. The results showeda sensitivity of 85.2%, specificity of 75%, positive predictive value of 88.5%, negative predictive value of 69.2% and accuracy of 82%.Levels of serum sdLDL were associated with severe to extensive stenosis degree, and showed a good diagnostic value, thus, it can beused for screening to determine the presence of coronary stenosis.

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Clinical Assessment of Three Common Tests for Superior Labral Anterior-Posterior Lesions

The American Journal of Sports Medicine ◽

10.1177/03635465020300061001 ◽

2002 ◽

Vol 30 (6) ◽

pp. 810-815 ◽

Cited By ~ 128

Author(s):

Edward G. McFarland ◽

Tae Kyun Kim ◽

Richard M. Savino

Keyword(s):

Positive Predictive Value ◽

Predictive Value ◽

Shoulder Arthroscopy ◽

Control Group ◽

Type I ◽

Specific Test ◽

Slide Test ◽

Posterior Lesion ◽

Sensitivity Specificity ◽

Anterior Posterior

Background Three tests (active compression, anterior slide, and compression rotation) are commonly used to diagnose superior labral anterior-posterior lesions. Hypothesis We hypothesized that the accuracy, sensitivity, and specificity for these tests was less than that previously reported and that a click in the shoulder during manipulation was not specific for the study lesion. Study Design Case-control study. Methods The three tests were performed on 426 patients who subsequently underwent shoulder arthroscopy. The results of physical examination were compared with the arthroscopic findings and analyzed for sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy. Results At arthroscopy, 39 patients had type II to IV lesions (study group); the remaining 387 patients had type I lesion or no lesion (control group). The incidences of positive results were not statistically different between the groups (P > 0.05). Our findings were as follows: most sensitive test, active compression (47%); most specific test, anterior slide (84%); highest positive predictive value, active compression (10%); highest overall accuracy, anterior slide test (77%); lowest overall accuracy, active compression test (54%). The presence of a click and the location of the pain were not reliable diagnostic indicators. Conclusions The results of such tests should be interpreted with caution when considering surgery for a possible superior labral anterior-posterior lesion.

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