scholarly journals Three Circulating Long Non-Coding RNAs Act as Biomarkers for Predicting NSCLC

2015 ◽  
Vol 37 (3) ◽  
pp. 1002-1009 ◽  
Author(s):  
Qingfeng Tang ◽  
Zhenhua Ni ◽  
Zhuoan Cheng ◽  
Jianhua Xu ◽  
Hui Yu ◽  
...  
Keyword(s):  
Predictive Value ◽  
Tumor Biology ◽  
Area Under The Curve ◽  
Rt Pcr ◽  
Small Cell Lung ◽  
Freezing And Thawing ◽  
Detection Analysis ◽  
Multi Stage ◽  
Potential Biomarker ◽  
Non Coding Rnas

Background/Aims: Circulating long non coding RNAs (lncRNAs) have emerged recently as major players in tumor biology and may be used for cancer diagnosis, prognosis, and as potential therapeutic targets. We explored circulating lncRNA as a predictor for the tumorigenesis of non-small-cell lung cancer (NSCLC). Methods: In this study, we applied a lncRNA microarray to screen for a potential biomarker for NSCLC, utilizing RT-PCR (ABI 7900HT). A multi-stage validation and risk score formula detection analysis was used. Results: We discovered that three lncRNAs (RP11-397D12.4, AC007403.1, and ERICH1-AS1) were up regulated in NSCLC, compared with cancer-free controls, with the merged area under the curve in the training and validation sets of 0.986 and 0.861. Furthermore, the positive predictive value and negative predictive value of the three merged factors were 0.72 and 0.87. We confirmed stable detection of the three lncRNAs by three cycles of freezing and thawing. Conclusions: RP11-397D12.4, AC007403.1, and ERICH1-AS1 may be potential biomarkers for predicting the tumorigenesis of NSCLC in the future.

scholarly journals Circulating microRNA-197-3p as a potential biomarker for asbestos exposure

2021 ◽  
Author(s):  
FRANCESCA FRONTINI ◽  
Ilaria Bononi ◽  
Elena Torreggiani ◽  
Giulia Di Mauro ◽  
Elisa Mazzoni ◽  
...  
Keyword(s):  
Asbestos Exposure ◽  
Inverse Correlation ◽  
Environmental Pollutant ◽  
Circulating Microrna ◽  
Rt Pcr ◽  
Liquid Biopsies ◽  
Potential Biomarker ◽  
Non Coding Rnas ◽  
Low Exposure ◽  
Prognostic And Predictive Markers

Asbestos is considered the main cause of diseases in workers exposed to this mineral in the workplace as well as an environmental pollutant. The association between asbestos and the onset of different diseases has been reported, but asbestos exposure specific biomarkers are not known. MicroRNAs (miRNAs) are small, single-strand, non-coding RNAs, with potential value as diagnostic, prognostic, and predictive markers in liquid biopsies. Sera collected from workers ex-exposed to asbestos (WEA) fibers were compared with sera from healthy subjects (HS) of similar age, as liquid biopsies. The expression of the circulating miRNA 197-3p was investigated employing two different highly analytical PCR methods, i.e. RT-PCR and dd-PCR. MiR-197-3p levels were tested in sera from WEA compared to HS. MiR-197-3p tested dysregulated in sera from WEA (n=75) compared to HS (n=62). Indeed, miR-197-3p was found to be 2.6 times down-regulated in WEA vs. HS (p=0.0001***). In addition, an inverse correlation was detected between miR-197-3p expression level and cumulative asbestos exposure, being this miRNA down-regulated 2.1 times in WEA, with high cumulative asbestos exposure, compared to WEA with low exposure (p=0.0303*). Circulating miR-197-3p, found to be down regulated in sera from WEA, is proposed as a new potential biomarker of asbestos exposure.

scholarly journals COVID-19 risk score as a public health tool to guide targeted testing: A demonstration study in Qatar

2021 ◽  
Author(s):  
Laith J. Abu-Raddad ◽  
Soha Dargham ◽  
Hiam Chemaitelly ◽  
Peter Coyle ◽  
Zaina Al Kanaani ◽  
...  
Keyword(s):  
Public Health ◽  
Logistic Regression ◽  
Risk Score ◽  
Roc Curve ◽  
Predictive Value ◽  
Area Under The Curve ◽  
Rt Pcr ◽  
Non Invasive ◽  
Targeted Testing ◽  
Performance Diagnostics

AbstractBackgroundThe objective of this study was to develop a Coronavirus Disease 2019 (COVID-19) risk score to guide targeted RT-PCR testing in Qatar.MethodsThe Qatar national COVID-19 testing database was analyzed. This database includes a total of 2,688,232 RT-PCR tests conducted between February 5, 2020-January 27, 2021. Logistic regression analyses were implemented to identify predictors of infection and to derive the COVID-19 risk score, as a tool to identify those at highest risk of having the infection. Score cut-off was determined using the receiving operating characteristic (ROC) curve based on maximum sum of sensitivity and specificity. The score’s performance diagnostics were assessed.ResultsLogistic regression analysis identified age, sex, and nationality as significant predictors of infection and were included in the risk score. The score’s scoring points were lower for females compared to males and higher for specific nationalities. The ROC curve was generated and the area under the curve was estimated at 0.63 (95% CI: 0.63-0.63). The score had a sensitivity of 59.4% (95% CI: 59.1%-59.7%), specificity of 61.1% (95% CI: 61.1%-61.2%), a positive predictive value of 10.9% (95% CI: 10.8%-10.9%), and a negative predictive value of 94.9% (94.9%-95.0%). The risk score derived early in the epidemic, based on data until only April 21, 2020, had a performance comparable to that of a score based on a year-long testing.ConclusionsThe concept and utility of a COVID-19 risk score were demonstrated in Qatar. Such a public health tool, based on a set of non-invasive and easily captured variables can have considerable utility in optimizing testing and suppressing infection transmission, while maximizing efficiency and use of available resources.

Evaluation of the clot burden score (cbs) for acute ischemic stroke (ais) in intent-to-treat patients.

2019 ◽  
Vol 1 (1) ◽  
pp. 11-15 ◽  
Author(s):  
Sarah Yaziz ◽  
Ahmad Sobri Muda ◽  
Wan Asyraf Wan Zaidi ◽  
Nik Azuan Nik Ismail
Keyword(s):  
Ischemic Stroke ◽  
Clinical Outcome ◽  
Acute Ischemic Stroke ◽  
Predictive Value ◽  
Area Under The Curve ◽  
Rank Correlation ◽  
Treatment Decision ◽  
Roc Curves ◽  
Significant Negative Correlation ◽  
Clot Burden

Background : The clot burden score (CBS) is a scoring system used in acute ischemic stroke (AIS) to predict patient outcome and guide treatment decision. However, CBS is not routinely practiced in many institutions. This study aimed to investigate the feasibility of CBS as a relevant predictor of good clinical outcome in AIS cases. Methods:  A retrospective data collection and review of AIS patients in a teaching hospital was done from June 2010 until June 2015. Patients were selected following the inclusion and exclusion criteria. These patients were followed up after 90 days of discharge. The Modified Rankin scale (mRS) was used to assess their outcome (functional status). Linear regression Spearman Rank correlation was performed between the CBS and mRS. The quality performance of the correlations was evaluated using Receiver operating characteristic (ROC) curves. Results: A total of 89 patients with AIS were analysed, 67.4% (n=60) male and 32.6% (n=29) female. Twenty-nine (29) patients (33.7%) had a CBS ?6, 6 patients (6.7%) had CBS <6, while 53 patients (59.6%) were deemed clot free. Ninety (90) days post insult, clinical assessment showed that 57 (67.6%) patients were functionally independent, 27 (30.3%) patients functionally dependent, and 5 (5.6%) patients were deceased. Data analysis reported a significant negative correlation (r= -0.611, p<0.001). ROC curves analysis showed an area under the curve of 0.81 at the cut-off point of 6.5. This showed that a CBS of more than 6 predicted a good mRS clinical outcome in AIS patients; with sensitivity of 98.2%, specificity of 53.1%, positive predictive value (PPV) of 76%, and negative predictive value (NPV) of 21%. Conclusion: CBS is a useful additional variable for the management of AIS cases, and should be incorporated into the routine radiological reporting for acute ischemic stroke (AIS) cases.

Diagnostic Value of Real-Time Shear Wave Elastography in Diagnosing Thyroid Cancer

2018 ◽  
Vol 68 (12) ◽  
pp. 2818-2822
Author(s):  
Maria Cristina Oprea ◽  
Mihaela Vlad ◽  
Ioana Golu ◽  
Ioan Sporea ◽  
Lazar Fulger
Keyword(s):  
Shear Wave ◽  
Predictive Value ◽  
Thyroid Nodules ◽  
Imaging Techniques ◽  
Area Under The Curve ◽  
Thyroid Volume ◽  
Shear Wave Elastography ◽  
Maximum Diameter ◽  
Diagnostic Tools ◽  
Tissue Elasticity

Thyroid nodules are a common pathology found in 50 to 60% of otherwise healthy people. Diagnostic imaging techniques are help discriminating between benign and malignant nodules, while fine needle aspiration is still a gold standard. Shear wave elastography, a recent imaging technique, holds the promise to become reliable diagnostic tools and is currently used in combination with ultrasound. We here report data obtained in a series of 52 thyroid nodules analysed by means of elastography, as well as conventional and Doppler ultrasound. We found no differences in age, nodule and thyroid volume, length, width, thickness and maximum diameter between benign and malignant lesions. Several sonographic patterns are considered to be predictive of malignancy, out of which we only found the intranodular blood flow to be statistically significant. By the means of shear wave elastography we have first assessed tissue elasticities, which are shown in a range of colours, depending on tissue elasticity/stiffness. Then, we have measured and recorded four parameters automatically displayed by the system, namely SWE-mean, SWE-max, SWE-SD and SWE-ratio. Data analysis showed all these quantitative parameters had good sensitivity, specificity, positive predictive value, negative predictive value and area under the curve, as calculated by the ROC curve. As with these parameters, the cut-off points were lower than in literature, still able to indicate reliable diagnoses, which were confirmed by histopathological exam. Our conclusion is that shear wave elastography has great potential for reliably and accurately diagnosing thyroid malignancies.

scholarly journals Sphingolipid Analysis Indicate Lactosylceramide as a Potential Biomarker of Inflammatory Bowel Disease in Children

Biomolecules ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 1083
Author(s):  
Aleksandra Filimoniuk ◽  
Agnieszka Blachnio-Zabielska ◽  
Monika Imierska ◽  
Dariusz Marek Lebensztejn ◽  
Urszula Daniluk
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
High Performance ◽  
Area Under The Curve ◽  
Study Groups ◽  
Diagnostic Value ◽  
Serum Samples ◽  
Specificity And Sensitivity ◽  
Potential Biomarker ◽  
Inflammatory Bowel

An altered ceramide composition in patients with inflammatory bowel disease (IBD) has been reported recently. The aim of this study was to evaluate the concentrations of sphingolipids in the serum of treatment-naive children with newly diagnosed IBD and to determine the diagnostic value of the tested lipids in pediatric IBD. The concentrations of sphingolipids in serum samples were evaluated using a quantitative method, an ultra-high-performance liquid chromatography-tandem mass spectrometry in children with Crohn’s disease (CD) (n=34), ulcerative colitis (UC) (n = 39), and controls (Ctr) (n = 24). Among the study groups, the most significant differences in concentrations were noted for C16:0-LacCer, especially in children with CD compared to Ctr or even to UC. Additionally, the relevant increase in C20:0-Cer and C18:1-Cer concentrations were detected in both IBD groups compared to Ctr. The enhanced C24:0-Cer level was observed only in UC, while C18:0-Cer only in the CD group. The highest area under the curve (AUC), specificity, and sensitivity were determined for C16:0-LacCer in CD diagnosis. Our results suggest that the serum LacC16-Cer may be a potential biomarker that distinguishes children with IBD from healthy controls and differentiates IBD subtypes. In addition, C20:0-Cer and C18:0-Cer levels also seem to be closely connected with IBD.

scholarly journals Optimal Utility of H-Reflex RDD as a Biomarker of Spinal Disinhibition in Painful and Painless Diabetic Neuropathy

Diagnostics ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1247
Author(s):  
Anne Worthington ◽  
Alise Kalteniece ◽  
Maryam Ferdousi ◽  
Luca Donofrio ◽  
Shaishav Dhage ◽  
...  
Keyword(s):  
Diabetic Neuropathy ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Initial Response ◽  
Healthy Controls ◽  
Painful Diabetic Neuropathy ◽  
Stimulus Response ◽  
Rate Dependent ◽  
Potential Biomarker ◽  
Spinal Inhibition

Impaired rate-dependent depression of the Hoffman reflex (HRDD) is a potential biomarker of impaired spinal inhibition in patients with painful diabetic neuropathy. However, the optimum stimulus-response parameters that identify patients with spinal disinhibition are currently unknown. We systematically compared HRDD, performed using trains of 10 stimuli at five stimulation frequencies (0.3, 0.5, 1, 2 and 3 Hz), in 42 subjects with painful and 62 subjects with painless diabetic neuropathy with comparable neuropathy severity, and 34 healthy controls. HRDD was calculated using individual and mean responses compared to the initial response. At stimulation frequencies of 1, 2 and 3 Hz, HRDD was significantly impaired in patients with painful diabetic neuropathy compared to patients with painless diabetic neuropathy for all parameters and for most parameters when compared to healthy controls. HRDD was significantly enhanced in patients with painless diabetic neuropathy compared to controls for responses towards the end of the 1 Hz stimulation train. Receiver operating characteristic curve analysis in patients with and without pain showed that the area under the curve was greatest for response averages of stimuli 2–4 and 2–5 at 1 Hz, AUC = 0.84 (95%CI 0.76–0.92). Trains of 5 stimuli delivered at 1 Hz can segregate patients with painful diabetic neuropathy and spinal disinhibition, whereas longer stimulus trains are required to segregate patients with painless diabetic neuropathy and enhanced spinal inhibition.

scholarly journals Tumor mutational burden assessment in non-small-cell lung cancer samples: results from the TMB2 harmonization project comparing three NGS panels

2021 ◽  
Vol 9 (5) ◽  
pp. e001904
Author(s):  
Javier Ramos-Paradas ◽  
Susana Hernández-Prieto ◽  
David Lora ◽  
Elena Sanchez ◽  
Aranzazu Rosado ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Predictive Value ◽  
Predictive Biomarker ◽  
Small Cell ◽  
Small Cell Lung ◽  
Mutational Burden ◽  
Reproducibility Study ◽  
Tumor Mutational Burden

BackgroundTumor mutational burden (TMB) is a recently proposed predictive biomarker for immunotherapy in solid tumors, including non-small cell lung cancer (NSCLC). Available assays for TMB determination differ in horizontal coverage, gene content and algorithms, leading to discrepancies in results, impacting patient selection. A harmonization study of TMB assessment with available assays in a cohort of patients with NSCLC is urgently needed.MethodsWe evaluated the TMB assessment obtained with two marketed next generation sequencing panels: TruSight Oncology 500 (TSO500) and Oncomine Tumor Mutation Load (OTML) versus a reference assay (Foundation One, FO) in 96 NSCLC samples. Additionally, we studied the level of agreement among the three methods with respect to PD-L1 expression in tumors, checked the level of different immune infiltrates versus TMB, and performed an inter-laboratory reproducibility study. Finally, adjusted cut-off values were determined.ResultsBoth panels showed strong agreement with FO, with concordance correlation coefficients (CCC) of 0.933 (95% CI 0.908 to 0.959) for TSO500 and 0.881 (95% CI 0.840 to 0.922) for OTML. The corresponding CCCs were 0.951 (TSO500-FO) and 0.919 (OTML-FO) in tumors with <1% of cells expressing PD-L1 (PD-L1<1%; N=55), and 0.861 (TSO500-FO) and 0.722 (OTML-FO) in tumors with PD-L1≥1% (N=41). Inter-laboratory reproducibility analyses showed higher reproducibility with TSO500. No significant differences were found in terms of immune infiltration versus TMB. Adjusted cut-off values corresponding to 10 muts/Mb with FO needed to be lowered to 7.847 muts/Mb (TSO500) and 8.380 muts/Mb (OTML) to ensure a sensitivity >88%. With these cut-offs, the positive predictive value was 78.57% (95% CI 67.82 to 89.32) and the negative predictive value was 87.50% (95% CI 77.25 to 97.75) for TSO500, while for OTML they were 73.33% (95% CI 62.14 to 84.52) and 86.11% (95% CI 74.81 to 97.41), respectively.ConclusionsBoth panels exhibited robust analytical performances for TMB assessment, with stronger concordances in patients with negative PD-L1 expression. TSO500 showed a higher inter-laboratory reproducibility. The cut-offs for each assay were lowered to optimal overlap with FO.

scholarly journals Gene expression-based biomarkers designating glioblastomas resistant to multiple treatment strategies

2021 ◽  
Author(s):  
Otília Menyhárt ◽  
János Tibor Fekete ◽  
Balázs Győrffy
Keyword(s):  
Gene Expression ◽  
Treatment Strategies ◽  
Area Under The Curve ◽  
Predictive Biomarkers ◽  
Subsequent Treatment ◽  
Survival Status ◽  
Multiple Treatment ◽  
Post Surgery ◽  
Potential Biomarker ◽  
Elevated Expression

Abstract Despite advances in molecular characterization of glioblastoma multiforme (GBM), only a handful of predictive biomarkers exist with limited clinical relevance. We aimed to identify differentially expressed genes in tumor samples collected at surgery associated with response to subsequent treatment, including temozolomide (TMZ) and nitrosoureas. Gene expression was collected from multiple independent datasets. Patients were categorized as responders/nonresponders based on their survival status at 16 months post-surgery. For each gene, the expression was compared between responders and nonresponders with a Mann-Whitney U test and receiver operating characteristic. The package "roc" was used to calculate the area under the curve (AUC). The integrated database comprises 454 GBM patients from three independent datasets and 10,103 genes. The highest proportion of responders (68%) were among patients treated with TMZ combined with nitrosoureas, where FCGR2B upregulation provided the strongest predictive value (AUC=0.72, p &lt; 0.001). Elevated expression of CSTA and MRPS17 was associated with a lack of response to multiple treatment strategies. DLL3 upregulation was present in subsequent responders to any treatment combination containing TMZ. Three genes (PLSCR1, MX1, and MDM2) upregulated both in the younger cohort and in patients expressing low MGMT delineate a subset of patients with worse prognosis within a population generally associated with a favorable outcome. The identified transcriptomic changes provide biomarkers of responsiveness, offer avenues for preclinical studies, and may enhance future GBM patient stratifications. The described methodology provides a reliable pipeline for the initial testing of potential biomarker candidates for future validation studies.

scholarly journals Triage of Patients Suspected of COVID-19 in Chronic Hemodialysis: Eosinophil Count Differentiates Low and High Suspicion of COVID-19

2020 ◽  
Vol 10 (1) ◽  
pp. 4
Author(s):  
Romain Vial ◽  
Marion Gully ◽  
Mickael Bobot ◽  
Violaine Scarfoglière ◽  
Philippe Brunet ◽  
...  
Keyword(s):  
Predictive Value ◽  
Eosinophil Count ◽  
Characteristic Curve ◽  
Final Analysis ◽  
Hemodialysis Patients ◽  
Chronic Hemodialysis ◽  
Screening Methods ◽  
Dialysis Session ◽  
Diagnostic Study ◽  
Rt Pcr

Background: Daily management to shield chronic dialysis patients from SARS-CoV-2 contamination makes patient care cumbersome. There are no screening methods to date and a molecular biology platform is essential to perform RT-PCR for SARS-CoV-2; however, accessibility remains poor. Our goal was to assess whether the tools routinely used to monitor our hemodialysis patients could represent reliable and quickly accessible diagnostic indicators to improve the management of our hemodialysis patients in this pandemic environment. Methods: In this prospective observational diagnostic study, we recruited patients from La Conception hospital. Patients were eligible for inclusion if suspected of SARS-CoV-2 infection when arriving at our center for a dialysis session between March 12th and April 24th 2020. They were included if both RT-PCR result for SARS-CoV-2 and cell blood count on the day that infection was suspected were available. We calculated the area under the curve (AUC) of the receiver operating characteristic curve. Results: 37 patients were included in the final analysis, of which 16 (43.2%) were COVID-19 positive. For the day of suspected COVID-19, total leukocytes were significantly lower in the COVID-19 positive group (4.1 vs. 7.4 G/L, p = 0.0072) and were characterized by lower neutrophils (2.7 vs. 5.1 G/L, p = 0.021) and eosinophils (0.01 vs. 0.15 G/L, p = 0.0003). Eosinophil count below 0.045 G/L identified SARS-CoV-2 infection with AUC of 0.9 [95% CI 0.81—1] (p < 0.0001), sensitivity of 82%, specificity of 86%, a positive predictive value of 82%, a negative predictive value of 86% and a likelihood ratio of 6.04. Conclusions: Eosinophil count enables rapid routine screening of symptomatic chronic hemodialysis patients suspected of being COVID-19 within a range of low or high probability.

scholarly journals Predictive value of pretreatment PD-L1 expression in EGFR-mutant non-small cell lung cancer: a meta-analysis

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhiyu Peng ◽  
Huahang Lin ◽  
Ke Zhou ◽  
Senyi Deng ◽  
Jiandong Mei
Keyword(s):  
Lung Cancer ◽  
Sensitivity Analysis ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Predictive Value ◽  
Meta Analysis ◽  
Small Cell ◽  
Small Cell Lung ◽  
Egfr Mutant ◽  
Egfr Tkis

Abstract Objective To investigate the predictive value of programmed death-ligand 1 (PD-L1) expression in non-small cell lung cancer (NSCLC) patients treated with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs). Methods We conducted a systemic search of PubMed, EMBASE, and the Cochrane Library from 1 January 2000 to 30 August 2020, to identify related studies. We combined the hazard ratio (HR) and 95% confidence interval (CI) to assess the correlation of PD-L1 expression with progression-free survival (PFS) and overall survival (OS). We assessed the quality of the included studies by the Newcastle–Ottawa Scale (NOS). We performed subgroup analyses based on immunohistochemistry (IHC) scoring system, IHC antibodies, sample size, countries, and survival analysis mode. Sensitivity analysis and evaluation of publication bias were also performed. Results Twelve studies including 991 patients met the criteria. The mean NOS score was 7.42 ± 1.19. Patients with high PD-L1 expression was associated with poorer PFS (HR = 1.90; 95% CI = 1.16–3.10; P = 0.011), while there was no association between PD-L1 expression and OS (HR = 1.19; 95% CI = 0.99–1.43; P = 0.070). Subgroup analysis prompted IHC scoring systems, IHC antibodies, and sample size have important effects on heterogeneity. The pooled results were robust according to the sensitivity analysis. Conclusions The result of this meta-analysis suggested that PD-L1 expression might be a predictive biomarker for EGFR-mutant non-small cell lung cancer treated with EGFR-TKIs.

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