The clinical role of microRNA-21 as a promising biomarker in the diagnosis and prognosis of colorectal cancer: a systematic review and meta-analysis.
ABSTRACT: This systematic analysis aimed to investigate the value of microRNA-21 (miR-21) in colorectal cancer for multiple purposes, including diagnosis and prognosis, as well as its predictive power in combination biomarkers. Fifty-seven eligible studies were included in our meta-analysis, including 25 studies for diagnostic meta-analysis and 32 for prognostic meta-analysis. For the diagnostic meta-analysis of miR-21 alone, the overall pooled results for sensitivity, specificity, and area under the curve (AUC) were 0.64 (95% CI: 0.53-0.74), 0.85 (0.79-0.90), and 0.85 (0.81-0.87), respectively. Circulating samples presented corresponding values of 0.72 (0.63-0.79), 0.84 (0.78-0.89), and 0.86 (0.83-0.89), respectively. For the diagnostic meta-analysis of miR-21-related combination biomarkers, the above three parameters were 0.79 (0.69-0.86), 0.79 (0.68-0.87), and 0.86 (0.83-0.89), respectively. Notably, subgroup analysis suggested that miRNA combination markers in circulation exhibited high predictive power, with sensitivity of 0.85 (0.70-0.93), specificity of 0.86 (0.77-0.92), and AUC of 0.92 (0.89-0.94). For the prognostic meta-analysis, patients with higher expression of miR-21 had significant shorter disease-free survival [DFS; pooled hazard ratio (HR): 1.60; 95% CI: 1.20-2.15] and overall survival (OS; 1.54; 1.27-1.86). The combined HR in tissues for DFS and OS were 1.76 (1.31-2.36) and 1.58 (1.30-1.93), respectively. Our comprehensive systematic review revealed that circulating miR-21 may be suitable as a diagnostic biomarker, while tissue miR-21 could be a prognostic marker for colorectal cancer. In addition, miRNA combination biomarkers may provide a new approach for clinical application.
Project description:Background:Arterial spin labeling is an MR imaging technique that measures cerebral blood flow (CBF) non-invasively. The aim of the study is to assess the diagnostic performance of arterial spin labeling (ASL) MR imaging for differentiation between high-grade glioma and low-grade glioma. Methods:Cochrane Library, Embase, Medline, and Web of Science Core Collection were searched. Study selection ended November 2017. This study was prospectively registered in PROSPERO (CRD42017080885). Two authors screened all titles and abstracts for possible inclusion. Data were extracted independently by 2 authors. Bivariate random effects meta-analysis was used to describe summary receiver operating characteristics. Trial sequential analysis (TSA) was performed. Results:In total, 15 studies with 505 patients were included. The diagnostic performance of ASL CBF for glioma grading was 0.90 with summary sensitivity 0.89 (0.79-0.90) and specificity 0.80 (0.72-0.89). The diagnostic performance was similar between pulsed ASL (AUC 0.90) with a sensitivity 0.85 (0.71-0.91) and specificity 0.83 (0.69-0.92) and pseudocontinuous ASL (AUC 0.88) with a sensitivity 0.86 (0.79-0.91) and specificity 0.80 (0.65-0.87). In astrocytomas, the diagnostic performance was 0.89 with sensitivity 0.86 (0.79 to 0.91) and specificity 0.79 (0.63 to 0.89). Sensitivity analysis confirmed the robustness of the findings. TSA revealed that the meta-analysis was adequately powered. Conclusion:Arterial spin labeling MR imaging had an excellent diagnostic accuracy for differentiation between high-grade and low-grade glioma. Given its low cost, non-invasiveness, and efficacy, ASL MR imaging should be considered for implementation in the routine workup of patients with glioma.
Project description:Conflicting results have been widely reported on the use of Golgi protein 73 (GP73) as a serum biomarker for diagnosing hepatocellular carcinoma (HCC). This study evaluated the accuracy of GP73, alpha-fetoprotein (AFP), and GP73 + AFP for diagnosing HCC. The meta-analysis was performed on 11 studies that were selected by means of a comprehensive systematic literature review. Summary diagnostic accuracy, meta-regression analysis for heterogeneity and publication bias, and other statistical analyses were performed using Meta-Disc (version 1.4) and Stata (version 12.0). Pooled sensitivity, specificity, and diagnostic odds ratio were 0.77 (95% CI: 0.75-0.79), 0.91 (95% CI: 0.90-0.92), and 12.49 (95% CI: 4.91-31.79) for GP73; 0.62 (95% CI: 0.60-0.64), 0.84 (95% CI: 0.83-0.85), and 11.61 (95% CI: 8.02-16.81) for AFP; and 0.87 (95% CI: 0.85-0.89), 0.85 (95% CI: 0.84-0.86), and 30.63 (95% CI: 18.10-51.84) for GP73 + AFP. The area under the curve values were 0.86, 0.84, and 0.91 for GP73, AFP, and GP73 + AFP, respectively. These results indicate that for HCC diagnosis, the accuracy of GP73 was higher than that of AFP, and that GP73 + AFP exhibited significantly higher diagnostic accuracy than did GP73 or AFP alone.
Project description:BACKGROUND:Acoustic radiation force impulse (ARFI) imaging is an ultrasound-based elastography method that has been studied in the staging of hepatic fibrosis, especially in chronic hepatitis. However, the diagnostic accuracy of ARFI in non-viral hepatopathies, such as autoimmune hepatitis and non-alcoholic fatty liver disease, has not been systematically determined. AIM:To systematically assess the diagnostic accuracy of ARFI in non-viral hepatopathies. METHODS:The databases of PubMed, Embase, Cochrane Library and clinicaltrials.gov were systematically searched for candidate studies reporting the diagnostic accuracy of ARFI for hepatic fibrosis. The pooled estimates of the sensitivity, specificity, diagnostic odds ratio, and positive and negative likelihood ratios were calculated with the summary receiver operating curve (sROC) performed using STATA software. RESULTS:In detail, a total of 29 diagnostic studies were included for further analysis. The quality of the included studies was relatively high using QUADAS method. The pooled sensitivity and specificity were 0.79 (0.73, 0.83) and 0.81 (0.75, 0.86), with AUROC 0.87 (0.83, 0.89) for the staging of significant fibrosis (F?2). Meanwhile, for the staging of severe fibrosis (F?3), the pooled sensitivity and specificity were 0.92 (0.87, 0.95) and 0.85 (0.80, 0.89), with AUROC 0.94 (0.92, 0.96). Furthermore, the pooled sensitivity and specificity were 0.89 (0.79, 0.95) and 0.89 (0.85, 0.92), with AUROC 0.94 (0.92, 0.96) for ARFI in staging cirrhosis (F = 4), which were similar to the data for severe fibrosis. No significant publication bias was present in this study. CONCLUSION:This meta-analysis demonstrated that ARFI exerted satisfactory diagnostic performance in staging non-viral hepatic fibrosis, especially severe fibrosis (F?3) and cirrhosis (F = 4).
Project description:Human pepsinogens are considered promising serological biomarkers for the screening of atrophic gastritis (AG) and gastric cancer (GC). However, there has been controversy in the literature with respect to the validity of serum pepsinogen (SPG) for the detection of GC and AG. Consequently, we conducted a systematic review and meta-analysis to assess the diagnostic accuracy of SPG in GC and AG detection.We searched PubMed, Embase, and the Chinese National Knowledge Infrastructure (CNKI) for correlative original studies published up to September 30, 2014. The summary sensitivity, specificity, positive diagnostic likelihood ratio (DLR+), negative diagnostic likelihood ratio (DLR-), area under the summary receiver operating characteristic curve (AUC) and diagnostic odds ratio (DOR) were used to evaluate SPG in GC and AG screening based on bivariate random effects models. The inter-study heterogeneity was evaluated by the I2 statistics and publication bias was assessed using Begg and Mazumdar's test. Meta-regression and subgroup analyses were performed to explore study heterogeneity.In total, 31 studies involving 1,520 GC patients and 2,265 AG patients were included in the meta-analysis. The summary sensitivity, specificity, DLR+, DLR-, AUC and DOR for GC screening using SPG were 0.69 (95% CI: 0.60-0.76), 0.73 (95% CI: 0.62-0.82), 2.57 (95% CI: 1.82-3.62), and 0.43 (95% CI: 0.34-0.54), 0.76 (95% CI: 0.72-0.80) and 6.01 (95% CI: 3.69-9.79), respectively. For AG screening, the summary sensitivity, specificity, DLR+, DLR-, AUC and DOR were 0.69 (95% CI: 0.55-0.80), 0.88 (95% CI: 0.77-0.94), 5.80 (95% CI: 3.06-10.99), and 0.35 (95% CI: 0.24-0.51), 0.85 (95% CI: 0.82-0.88) and 16.50 (95% CI: 8.18-33.28), respectively. In subgroup analysis, the use of combination of concentration of PGI and the ratio of PGI:PGII as measurement of SPG for GC screening yielded sensitivity of 0.70 (95% CI: 0.66-0.75), specificity of 0.79 (95% CI: 0.79-0.80), DOR of 6.92 (95% CI: 4.36-11.00), and AUC of 0.78 (95% CI: 0.72-0.81), while the use of concentration of PGI yielded sensitivity of 0.55 (95% CI: 0.51-0.60), specificity of 0.79 (95% CI: 0.76-0.82), DOR of 6.88 (95% CI: 2.30-20.60), and AUC of 0.77 (95% CI: 0.73-0.92). For AG screening, the use of ratio of PGI:PGII as measurement of SPG yielded sensitivity of 0.69 (95% CI: 0.52-0.83), specificity of 0.84 (95% CI: 0.68-0.93), DOR of 11.51 (95% CI: 6.14-21.56), and AUC of 0.83 (95% CI: 0.80-0.86), the use of combination of concentration of PGI and the ratio of PGI:PGII yield sensitivity of 0.79 (95% CI: 0.72-0.85), specificity of 0.89 (95% CI: 0.85-0.93), DOR of 24.64 (95% CI: 6.95-87.37), and AUC of 0.87 (95% CI: 0.81-0.92), concurrently, the use of concentration of PGI yield sensitivity of 0.46 (95% CI: 0.38-0.54), specificity of 0.93 (95% CI: 0.91-0.95), DOR of 19.86 (95% CI: 0.86-456.91), and AUC of 0.86 (95% CI: 0.52-1.00).SPG has great potential as a noninvasive, population-based screening tool in GC and AG screening. In addition, given the potential publication bias and high heterogeneity of the included studies, further high quality studies are required in the future.
Project description:Previous researches pointed out that the measurement of urine fibronectin (Fn) could be a potential diagnostic test for bladder cancer (BCa). We conducted this meta-analysis to fully assess the diagnostic value of urine Fn for BCa detection.A systematic literature search in PubMed, ISI Web of Science, EMBASE, Cochrane library, and CBM was carried out to identify eligible studies evaluating the urine Fn in diagnosing BCa. Pooled sensitivity, specificity, and diagnostic odds ratio (DOR) with their 95% confidence intervals (CIs) were calculated, and summary receiver operating characteristic (SROC) curves were established. We applied the STATA 13.0, Meta-Disc 1.4, and RevMan 5.3 software to the meta-analysis.Eight separate studies with 744 bladder cancer patients were enrolled in this meta-analysis. The pooled sensitivity, specificity, and DOR were 0.80 (95%CI = 0.77-0.83), 0.79 (95%CI = 0.73-0.84), and 15.18 (95%CI = 10.07-22.87), respectively, and the area under the curve (AUC) of SROC was 0.83 (95%CI = 0.79-0.86). The diagnostic power of a combined method (urine Fn combined with urine cytology) was also evaluated, and its sensitivity and AUC were significantly higher (0.86 (95%CI = 0.82-0.90) and 0.89 (95%CI = 0.86-0.92), respectively). Meta-regression along with subgroup analysis based on various covariates revealed the potential sources of the heterogeneity and the detailed diagnostic value of each subgroup. Sensitivity analysis supported that the result was robust. No threshold effect and publication bias were found in this meta-analysis.Urine Fn may become a promising non-invasive biomarker for bladder cancer with a relatively satisfactory diagnostic power. And the combination of urine Fn with cytology could be an alternative option for detecting BCa in clinical practice. The potential value of urine Fn still needs to be validated in large, multi-center, and prospective studies.
Project description:<h4>Background</h4>The aim of our study was to assess the value of serum human epididymis protein 4 (HE4) to diagnose lung cancer and provide reliable scientific conclusions to guide clinical practice.<h4>Methods</h4>A systematic search of the PubMed, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature, and WANFANG databases was conducted to identify all studies examining serum HE4 in the diagnosis of lung cancer published up to June, 2017. The Quality Assessment of Diagnostic Accuracy Studies tool was used to evaluate the methodological quality of each trial. The meta-analysis was performed using STATA software and Review Manager 5.3.<h4>Results</h4>There were 21 studies involving 1883 cases and 1696 controls included in our meta-analysis. The pooled sensitivity and specificity of HE4 for diagnosing lung cancer were 0.73 (95% confidence interval [CI] 0.68-0.78) and 0.86 (95% CI 0.81-0.91), respectively. The positive likelihood ratio and negative likelihood ratio were 5.4 (95% CI 3.8-7.5) and 0.31 (95% CI 0.26-0.37), respectively. The diagnostic odds ratio was 17 (95% CI 12-26). The area under the curve of the summary receiver-operating characteristic curve was 0.86 (95% CI 0.83-0.89). Race, assay method, type of cancer, sample size, and publication date might be sources of heterogeneity in our meta-analysis. Subgroup analyses showed that the sensitivity in Caucasians was higher than that in Asians (0.81, 95% CI 0.71-0.91; and 0.71, 95% CI 0.66-0.77, respectively), but the specificity in Asians was better than that in Caucasians (0.87, 95% CI 0.81-0.92; and 0.85, 95% CI 0.73-0.97, respectively). The chemiluminescent microparticle immunoassay had the highest sensitivity, with 0.79 (95% CI 0.73-0.97), and the enzyme-linked immunosorbent assay had the highest specificity, with 0.87 (95% CI 0.79-0.94). HE4 had high diagnostic efficacy when screening for small cell lung cancer with the highest specificity (0.90, 95% CI 0.77-1.00).<h4>Conclusions</h4>HE4 is a relatively promising and effective biomarker for the diagnosis of lung cancer. Furthermore, given the limitations of our study, additional large-scale and well-designed studies are needed in the future.
Project description:Background:Fractional flow reserve (FFR), as a functional measurement of coronary stenosis, is recommended for guiding revascularization in intermediate coronary lesions. However, it still remains underutilized for potential reasons including time consumption, costs, or contraindications associated with adenosine administration. Here we performed this meta-analysis to assess the diagnostic performance of two adenosine-free indices, instantaneous wave free-ratio (iFR), and quantitative flow ratio (QFR) in evaluating coronary stenosis severity with FFR as the reference standard. Methods:PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched to include relevant studies with the diagnostic accuracy of iFR or QFR referenced to FFR. A bivariate model was applied to pool diagnostic parameters. We used Cochran's Q test and I2 index to assess heterogeneity and identify the potential source of heterogeneity by meta-regression. Results:A total of 8213 lesions from 28 studies (19 for iFR and 9 for QFR) were included in this meta-analysis. The pooled sensitivity and specificity were 0.79 (95% CI, 0.75 to 0.83) and 0.85 (95% CI, 0.82 to 0.87) for iFR and 0.90 (95% CI, 0.84 to 0.93) and 0.88 (95% CI, 0.86 to 0.90) for QFR, respectively. Significantly higher sensitivity and specificity were observed in the bivariate analysis for QFR than for iFR (P < 0.001 for both). The area under summary receiver-operating curve of iFR and QFR was 0.89 (95% CI, 0.86 to 0.92) and 0.92 (95% CI, 0.89 to 0.94). Conclusion:Evidence suggests that both of the two indices have good performance in detecting functional ischemia of coronary arteries and QFR might be a promising method without requiring the pressure wire. Further application of QFR may potentially provide important information to clinicians in the assessment of coronary lesions.
Project description:Background: Numerous studies have suggested that differentially expressed miRNAs may be promising diagnostic markers for pancreatic cancer (PC), but the results are inconsistent. We aimed to summarize the diagnostic accuracy of circulating miRNAs, carbohydrate antigen 19-9 (CA19-9), and the combination of miRNAs and CA19-9. Material and Methods: A literature search of online databases including PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI) and WanFang was conducted. Relative data were extracted from eligible included studies, and a meta-analysis was performed. Results: A total of 46 studies involving 4,326 PC patients and 4,277 non-PC controls were included. The pooled sensitivity (SEN), specificity (SPE) and AUC of the circulating miRNAs for differentiating PC patients from non-PC controls were 0.79 (0.77-0.81), 0.77 (0.75-0.79), and 0.85 (0.81-0.87), respectively. The combination of miRNAs and CA19-9 greatly improved the SEN, SPE and AUC to 0.84 (0.80-0.87), 0.91 (0.89-0.93) and 0.94 (0.92-0.96), respectively. Moreover, circulating miRNAs also yielded an acceptable diagnostic accuracy for early-stage PC with a SEN of 0.79 (0.76-0.82), a SPE of 0.74 (0.68-0.79) and an AUC of 0.81 (0.77-0.84). Conclusion: Circulating miRNAs exhibited satisfactory diagnostic performance for PC and even early-stage PC. The combination of circulating miRNAs and CA19-9 can further improve the diagnostic accuracy, providing a novel strategy for PC diagnosis.
Project description:BACKGROUND:In recent years, many studies focused on the association between the microRNAs (miRNAs) and the risk of systemic lupus erythematosus (SLE), especially miRNA-21 (miR-21). We aimed to investigate the role of circulating miRNAs, especially the miR-21, as a biomarker in detecting SLE. METHODS:We searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and China National Knowledge Infrastructure through Mar 3th, 2019. We performed this meta-analysis in a fixed/random-effect model using Meta-disc 1.4 and STATA 15.1. RESULTS:A total of 17 relevant studies were eligible to analyze pooled accuracy. The overall performance of total mixed miRNAs (TmiRs) detection was: pooled sensitivity, 0.71 (95% confidence interval [CI], 0.69 to 0.72); pooled specificity, 0.81 (95%CI, 0.79 to 0.83); and area under the summary receiver operating characteristic curves value (SROC), 0.8797. The miR-21 detection was: pooled sensitivity, 0.68 (95%CI, 0.62 to 0.74); pooled specificity, 0.77 (95%CI, 0.69 to 0.84); and SROC, 0.8281. The meta-regression analysis showed that the type of samples was the sources of heterogeneity. The subgroup analysis suggested that detection in plasma group had the largest AUC of SROC in all the subgroups: pooled sensitivity, 0.8 (95%CI, 0.78 to 0.82); pooled specificity, 0.83 (95%CI, 0.8 to 0.86); and SROC, 0.9068. CONCLUSIONS:Our meta-analysis demonstrated that circulating miRNAs might be potential novel biomarkers for detecting SLE, especially miR-21. Moreover, plasma is recommended as the clinical specimen for diagnostic detection.
Project description:<h4>Objectives</h4>MicroRNA-21 in serum is a promising marker for the diagnosis of lung carcinoma. A meta-analysis was performed to assess the diagnostic accuracy and clinical value of serum microRNA-21 in patients with lung carcinoma.<h4>Methods</h4>PubMed, EMBASE, Web of Knowledge (ISI), the Cochrane Library, Scopus, BioMed Central, Science Direct, China National Knowledge Infrastructure (CNKI), Wan Fang data and Technology of Chongqing (VIP) databases were searched to identify studies in English and Chinese that assessed the diagnostic value of serum miR-21 for lung carcinoma, from inception to 9 April 2014. Two independent investigators identified and extracted the study characteristics from all articles according to defined inclusion and exclusion criteria. Quality assessment of diagnostic accuracy studies (QUADAS) was used to score the quality of the eligible studies. Stata12 and Meta-DiSc software were used to test the heterogeneity and to perform the meta-analysis.<h4>Results</h4>Our search returned 1008 articles, of which seven fulfilled the inclusion criteria, accounting for 500 patients and 386 controls. Using random-effect model analysis, the summary assessments revealed that the mean sensitivity was 0.71% (95%CI: 57-82%) and specificity was 0.84% (95%CI: 76-89%). The area under the receiver operating characteristic curve was 0.86 (95%CI: 0.83-0.89). In addition, heterogeneity was clearly apparent but was not caused by the threshold effect, as shown by Meta-DiSc analysis.<h4>Conclusion</h4>The current evidence suggests that serum miR-21 can be rapidly measured in lung carcinoma patients and has potential diagnostic value with moderate sensitivity and specificity. Further prospective studies to assess the early stage diagnostic value are needed in the future.