Clinical Diagnostic Implications of Body Fluid MiRNA in Oral Squamous Cell Carcinoma: A Meta-Analysis

Oral cancer, predominantly oral squamous cell carcinoma (OSCC), is one of the most leading causes of cancers worldwide. Due to a low 5-year survival rate, highly effective methods for the early detection of OSCC are totally needed. MicroRNAs (miRNAs), as promising biomarkers, can bring insights into tumorigenesis of oral cancers. However, studies on the accuracy of miRNAs detection in OSCC have inconsistent conclusions, leading us to conduct this meta-analysis. The aim of this study was to systematically review the articles investigating the diagnostic value of miRNAs in OSCC.The PubMed, Embase, Chinese National Knowledge Infrastructure (CNKI), Web of Science were searched (updated to June 11th, 2015) to identify all articles evaluating the diagnostic yield of miRNAs for OSCC. The pooled sensitivity, specificity, and other diagnostic parameters were used to assess the performance of miRNAs assays on OSCC detection. Statistical analysis was conducted by employing the R software.The present meta-analysis comprised 23 studies from 10 articles, including 598 OSCC patients and 320 healthy individuals, available for analysis. The summary receiver operator characteristic (SROC) curve was plotted. Meanwhile, the pooled diagnostic parameters and the area under curve (AUC) were calculated based on all included studies. The pooled diagnostic parameters calculated from all 23 studies were as follows: pooled sensitivity of 0.759 (95% CI: 0.701–0.809), pooled specificity of 0.773 (95% CI: 0.713–0.823) and AUC of 0.832, which indicates a relatively high diagnostic accuracy of miRNAs in differentiating OSCC patients from healthy controls. Meanwhile, In addition, subgroup analyses were conducted to access the heterogeneity between studies, which is based on specimen (serum/plasma/blood/saliva/ tissue) and ethnicity (Asian/Caucasian).In summary, our meta-analysis suggests that miRNAs might be used in noninvasive screening tests for OSCC, which needs further large-scale studies to be validated.     

Potential Role of Circulating MiR-21 in the Diagnosis and Prognosis of Digestive System Cancer: A Systematic Review and Meta-Analysis

Recent evidences indicate that circulating microRNAs (miRNAs) exhibit aberrant expression in the plasma of patients suffering from cancer compared to normal individuals, suggesting that it may be a useful noninvasion diagnostic method. MiR-21 plays crucial roles in carcinogenesis and can be served as a biomarker for the detection of various cancers. Therefore, the aim of this meta-analysis is to assess the potential role of miR-21 for digestive system cancer.By searching the PubMed, Embase, and Web of Science for publications concerning the diagnostic value of miR-21 for digestive system cancer, total of 23 publications were included in this meta-analysis. Receiver operating characteristic curves (ROC) were used to check the overall test performance. For prognostic meta-analysis, pooled hazard ratios (HRs) of circulating miR-21 for survival were calculated.Totally 23 eligible publications were included in this meta-analysis (15 articles for diagnosis and 8 articles for prognosis). For diagnostic meta-analysis, the summary estimates revealed that the pooled sensitivity and specificity were 0.76(95% CI = 0.70–0.82) and 0.84 (95% CI = 0.78–0.89). Besides, the area under the summary ROC curve (AUC) is 0.87. For prognostic meta-analysis, the pooled HR of higher miR-21 expression in circulation was 1.94 (95% CI = 0.99–3.82, P = 0.055), which indicated higher miR-21 expression could be likely to predict poorer survival in digestive system cancer. The subgroup analysis implied the higher expression of miR-21 was correlated with worse overall survival in the Asian population in digestive system cancer (HR = 2.41, 95% CI = 1.21–4.77, P = 0.012).The current evidence suggests circulating miR-21 may be suitable to be a diagnostic and prognostic biomarker for digestive system cancer in the Asians.     

胰腺癌患者血浆miR-155检测及其诊断价值

目的 检测胰腺癌患者血浆miR-155表达量,评价其对胰腺癌的诊断价值.方法 收集62例胰腺癌、61例慢性胰腺炎(CP)及36例正常对照者的血标本,抽提血浆RNA,应用实时PCR检测miR-155表达量,并分析其与胰腺癌临床参数的关系.应用接受者操作特征(ROC)曲线下面积(AUC)评价血浆miR-155表达量对胰腺癌的诊断价值.结果 胰腺癌、CP和正常对照组的血浆miR-155表达量分别为5.41±3.14、2.59±2.49和0.77±1.17,胰腺癌血浆miR-155表达量显著高于CP及正常对照组(P＜0.01).胰腺癌血浆miR-155表达量与患者年龄、性别、肿瘤大小等均无显著相关性,而与肿瘤TNM分期呈显著负相关(r=-0.323,P=0.01).经ROC分析,胰腺癌对正常对照组的AUC为0.943(95%CI0.902～0.985),敏感性和特异性分别为87.1%和83.3%;胰腺癌对CP的AUC为0.762(95%CI0.678～0.846),敏感性和特异性分别为64.5%和73.8%;胰腺癌对正常对照组+CP组的AUC为0.829(95%CI0.767～0.892),敏感性和特异性分别为62.9%和84.5%.结论 胰腺癌患者血浆miR-155表达量显著升高,对胰腺癌的诊断可能有一定的应用价值.     

Diagnostic accuracy of different computer-aided diagnostic systems for prostate cancer based on magnetic resonance imaging: A systematic review with diagnostic meta-analysis

Background:Computer-aided detection (CAD) system for accurate and automated prostate cancer (PCa) diagnosis have been developed, however, the diagnostic test accuracy of different CAD systems is still controversial. This systematic review aimed to assess the diagnostic accuracy of CAD systems based on magnetic resonance imaging for PCa.Methods:Cochrane library, PubMed, EMBASE and China Biology Medicine disc were systematically searched until March 2019 for original diagnostic studies. Two independent reviewers selected studies on CAD based on magnetic resonance imaging diagnosis of PCa and extracted the requisite data. Pooled sensitivity, specificity, and the area under the summary receiver operating characteristic curve were calculated to estimate the diagnostic accuracy of CAD system.Results:Fifteen studies involving 1945 patients were included in our analysis. The diagnostic meta-analysis showed that overall sensitivity of CAD system ranged from 0.47 to 1.00 and, specificity from 0.47 to 0.89. The pooled sensitivity of CAD system was 0.87 (95% CI: 0.76–0.94), pooled specificity 0.76 (95% CI: 0.62–0.85), and the area under curve (AUC) 0.89 (95% CI: 0.86–0.91). Subgroup analysis showed that the support vector machines produced the best AUC among the CAD classifiers, with sensitivity ranging from 0.87 to 0.92, and specificity from 0.47 to 0.95. Among different zones of prostate, CAD system produced the best AUC in the transitional zone than the peripheral zone and central gland; sensitivity ranged from 0.89 to 1.00, and specificity from 0.38 to 0.85.Conclusions:CAD system can help improve the diagnostic accuracy of PCa especially using the support vector machines classifier. Whether the performance of the CAD system depends on the specific locations of the prostate needs further investigation.     

Circulating MicroRNAs as Biomarkers in Hepatocellular Carcinoma Screening: A Validation Set From China

Hepatocellular carcinoma (HCC) is a global public health concern. Current diagnostic methods show poor performance in early-stage HCC detection. Accumulating evidences revealed the great potential of microRNAs (miRNAs) as noninvasive biomarkers in HCC detection. In this study, we examined the diagnostic performance of serum miR-10b, miR-106b, and miR-181a for HCC screening in China. Furthermore, a systematic review of previous related studies was conducted to confirm our results.One hundred eight participants including 27 HCC patients, 31 chronic liver disease (CLD) patients, and 50 healthy people were recruited in this study. Blood specimen was drawn from each participant to extract serum miRNAs. Statistical analyses were performed to assess the 3 miRNAs levels in HCC, CLD patients, and normal controls. A meta-analysis was conducted to further assess the diagnostic value of miRNAs in HCC detection based on previous studies.All these miRNAs (miR-10b, miR-181a, miR-106b) could well discriminate HCC patients from normal controls, with area under the receiver-operating characteristic curve (AUC) values of 0.85 (95% confidence interval [CI]: 0.76–0.94), 0.82 (95% CI: 0.72–0.91), and 0.89 (95% CI: 0.81–0.97), respectively. In addition, these miRNAs could distinguish HCC cases from CLD controls with a medium accuracy. However, the ability of these miRNAs in differentiating CLD patients from normal controls was not satisfactory. Panel of these miRNAs displayed a better performance compared with single miRNA assay, with AUC values of 0.94 (95% CI: 0.89–0.99) in discriminating HCC patients from normal controls and 0.91 (95% CI: 0.80–0.97) in discriminating HCC patients from CLD controls. Results of meta-analysis of previous studies combined with the current study suggested that circulating miRNAs could well differentiate HCC from normal controls, with AUC values of 0.86 (95% CI: 0.82–0.89) for single miRNA assay and 0.94 (95% CI: 0.91–0.96) for miRNA panel assay.Serum miR-10b, miR-106b, and miR-181a have great potential to serve as accurate and noninvasive biomarkers for HCC preliminary screening. Meta-analysis of previous studies combined with current study further confirmed that circulating miRNAs could play an important role in HCC detection. Further large-scale studies are needed to confirm the clinical significance of circulating miRNAs in HCC screening.     

CT-Base Pulmonary Artery Measurementin the Detection of Pulmonary Hypertension: A Meta-Analysis and Systematic Review

To summarize the performance of CT-based main pulmonary artery diameter or pulmonary artery to aorta ratio (PA:A ratio) measurement in detection of pulmonary hypertension by a systematic review and meta-analysis.A comprehensive literature search was performed to identify studies determining diagnostic accuracy of main pulmonary artery diameter or PA:A ratio measurement for pulmonary hypertension. The Quality Assessment of Diagnostic Accuracy Studies tool was used to assess the quality of the included studies. A bivariate random-effects model was used to pool sensitivity, specificity, positive/negative likelihood ratio (PLR/NLR), and diagnostic odds ratio (DOR). Summary receiver operating characteristic (SROC) curves and area under the curve (AUC) were used to summarize overall diagnostic performance.This meta-analysis included 20 publications involving 2134 subjects. Summary estimates for main pulmonary artery diameter measurement in the diagnosis of pulmonary hypertension were as follows: sensitivity, 0.79 (95% CI 0.72–0.84); specificity, 0.83 (95% CI 0.75–0.89); PLR, 4.68 (95% CI 3.13–6.99); NLR, 0.26 (95% CI 0.20–0.33); DOR, 18.13 (95% CI 10.87–30.24); and AUC 0.87. The corresponding summary performance estimates for using the PA:A ratio were as follows: sensitivity, 0.74 (95% CI 0.66–0.80); specificity, 0.81 (95% CI 0.74–0.86); PLR, 3.83 (95% CI, 2.70–5.43); NLR, 0.33 (95% CI 0.24–0.44); DOR, 11.77 (95% CI 6.60–21.00); and AUC 0.84.Both main pulmonary artery diameter and PA:A ratio are helpful for diagnosing pulmonary hypertension. Nevertheless, the results of pulmonary artery measurement should be interpreted in parallel with the results of traditional tests such as echocardiography.     

Diagnostic value of microRNA-155 in active tuberculosis: A systematic review and meta-analysis

Background:Tuberculosis (TB) is a preventable and treatable disease, but the increased mortality and morbidity associated with TB continues to be a leading cause of death globally. MicroRNA (miRNA)-155 has been recognized as a marker of many lung diseases. However, the effectiveness of this marker for diagnosing TB remains unclear.Methods:A detailed search (updated on February 6, 2021) of literature published in the Wanfang database, EMBASE, PubMed, CNKI, and Cochrane Library was conducted to identify eligible studies suitable for inclusion in the current research. The positive likelihood ratio, negative likelihood ratio, specificity, area under the curve, sensitivity, and diagnostic odds ratio were used to investigate the diagnostic potential of miRNA-155.Results:A total of 122 studies related to active TB, which completely complied with the inclusion and exclusion criteria of our meta-analysis, were included. The overall results suggested a moderately high diagnostic accuracy and efficacy of miRNA-155, with a specificity of 0.85 (95% confidence interval = 0.77–0.91) and sensitivity of 0.87 (95% confidence interval = 0.76–0.93). The result based on dysregulated status demonstrated that the upregulated group yielded better accuracy and efficacy than the downregulated group. Notably, the accuracy and efficacy of miRNA-155 in pediatric TB were higher than those in adult TB. The results showed that the accuracy and efficacy of miRNA-155 in children were higher than those in adults.Conclusion:The results of the meta-analysis suggested that miRNA-155 could serve as an effective biomarker for identifying active TB.     

粪便microRNAs检测用于胰腺癌筛查诊断的价值评价

目的 检测胰腺癌患者粪便microRNAs,评价其诊断价值.方法 收集29例胰腺癌患者、22例慢性胰腺炎(CP)患者以及13例健康志愿者的粪便标本,抽提粪便总RNA,应用实时定量PCR法检测各组样本miR-21、miR-155、miR-181a、miR-181b、miR-196a、miR-210的表达量,以miR-16作为内参基因.应用接受者操作特征(ROC)曲线(AUC)评估microRNAs对胰腺癌的诊断价值.结果 粪便总RNA抽提及microRNAs检测方法具有稳定及可重复性.胰腺癌组miR-181b、miR-196a、miR-210的表达量分别为2.22±0.64、2.78±0.14、5.55±0.38;CP组为1.42±0.39、3.88±0.85、5.39±0.69;对照组为0.32±0.40、1.14±0.98、4.23±0.99.胰腺癌组和CP组均较对照组显著增加(P值均＜0.05);而胰腺癌组与CP组间无显著差异.胰腺癌组对对照组的miR-181b AUC为0.745(95%CI 0.597～0.894),诊断胰腺癌的敏感性和特异性分别为84.6%和51.7%;miR-210的AUC为0.772(95%CI 0.629～0.914),对胰腺癌的诊断敏感性和特异性分别为84.6%和65.5%.两组比较差异均有统计学意义(P值均＜0.05).miR-196a对胰腺癌无诊断意义,但胰腺癌患者粪便miR-196a的表达与肿瘤直径相关(r=0.516,P=0.041).结论 粪便RNA的抽提和microRNAs检测为无创性,且具有可重复性.miR-181b和miR-210在胰腺癌患者粪便中的表达增高,有可能是胰腺癌潜在的分子标志物.     

Diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration for pancreatic cancer: A meta-analysis

Background and objectiveEUS-FNA of pancreatic lesion has been put into clinical use widely in many centers. The present meta-analysis was conducted to study the diagnostic role of EUS-FNA in pancreatic cancer.MethodsA comprehensive review of study on the precision of EUS-FNA in the diagnosis of pancreatic cancer. A random effects model was used to pool the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR). A summary receiver-operating characteristic (SROC) was constructed to summarize the overall test performance.ResultsThirty-one articles were eligible for the meta-analysis. The pooled sensitivity, specificity, PLR, NLR and DOR of EUS-FNA in the diagnosis of pancreatic cancer were 0.89 (95% CI: 0.88–0.90), 0.96 (95% CI: 0.95–0.97), 16.88 (95% CI: 10.63–26.79), 0.13 (95%CI: 0.10–0.16) and 150.80 (95%CI: 95.94–237.03) respectively. In subgroup meta-analysis of the prospective studies, the pooled sensitivity, specificity, PLR, NLR and DOR were 0.91 (95% CI: 0.90–0.93), 0.94 (95% CI: 0.91–0.96), 11.19 (95% CI: 6.36–19.69), 0.10 (95% CI: 0.07–0.15) and 125.22 (62.37–251.41). The area under the curve (AUC) was 0.97, indicating a good performance of overall accuracy.ConclusionEUS-FNA has the high sensitivity and specificity in differentiating pancreatic cancer. Moreover, it is also a safe diagnostic modality with little complications.     

Diagnostic value of microRNA-25 in patients with non-small cell lung cancer in Chinese population: A systematic review and meta-analysis

Objective:Previous studies have shown that microRNA-25 (miR-25) plays a key role in the occurrence and development of non-small cell lung cancer (NSCLC). Many studies have shown that there is a significant increment of miR-25 in circulating blood of patients with NSCLC. The meta-analysis aims to explore diagnostic value of miR-25 in NSCLC in Chinese population.Methods:PubMed, Web of science, Excerpta Medica Database, China national knowledge infrastructure and China Wanfang database were searched to collect studies upon correlation between miR-25 and diagnosis of the patients with NSCLC until April 2020. Combined sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and area under receiver operating characteristic curve were calculated by Stata 15.0 software. Literature assessment was conducted according to quality assessment of diagnostic accuracy studies, and documents with scores above or equal to 11 were included in this meta-analysis.Results:Six studies were included, including 480 cases with NSCLC and 451 healthy controls. The combined sensitivity (0.75, 95% confidence interval [CI]: 0.69∼0.80), specificity (0.81, 95% CI: 0.76∼0.86), positive likelihood ratio (4.04, 95% CI: 3.14∼5.20), negative likelihood ratio (0.31, 95% CI: 0.25∼0.37), diagnostic odds ratio (13.09, 95% CI: 9.37∼18.29) and area under curve (0.85, 95% CI: 0.82∼0.88) indicated that miR-25 had desirable diagnostic accuracy for NSCLC.Conclusion:MiR-25 can be applied in diagnosis of NSCLC and has potential of becoming a biomarker for detection of patients with early NSCLC in Chinese population.     

Exploring diagnostic and prognostic predictive values of microRNAs for acute myocardial infarction: A PRISMA-compliant systematic review and meta-analysis

Objective:Previous investigations yielded inconsistent results for diagnostic and prognostic predictive values of MicroRNAs (miRNAs) for acute myocardial infarction (AMI).Methods and results:We systematically searched on PubMed and Web of Science for articles explored association of miRNAs and AMI published from January 1989 to March 2019. For diagnostic studies, a summary of sensitivity, specificity, positive likelihood ratios (PLR), negative likelihood ratios (NLR), and diagnostic odds ratio (DOR), which indicated the accuracy of microRNAs in the differentiation of AMI and no AMI, were calculated from the true positive (TP), true negative (TN), false positive (FP), and false negative (FN) of each study. In addition, the summary receive-operating characteristics (SROC) curve was constructed to summarize the TP and FP rates. For follow-up study, we computed hazard ratios (HRs) and 95% confidence intervals (CIs) for individual clinical outcomes. The meta-analysis showed a sensitivity [0.72 (95% CI: 0.61--0.81)] and specificity [0.88 (95% CI: 0.79--0.94)] of miR-1 for AMI. In addition, miR-133 showed a sensitivity [0.73 (95% CI: 0.55--0.85)] and specificity [0.88 (95% CI: 0.74--0.95)] for AMI. Moreover, the present study showed a sensitivity [0.83 (95% CI: 0.74--0.89)] and specificity [0.96 (95% CI: 0.82--0.99)] of miR-208 for AMI. A significant association was found between miR-208 and mortality after AMI (HR 1.09, 95% CI 1.01--1.18). It also indicated a sensitivity [0.84 (95% CI: 0.70--0.92)] and specificity [0.97 (95% CI: 0.87--0.99)] of miR-499 for AMI.Conclusions:Circulating miR-1, miR-133, miR-208, and miR-499 showed diagnostic values in AMI.     

Association between miR-27a rs895819 polymorphism and breast cancer susceptibility: Evidence based on 6118 cases and 7042 controls

Background:Polymorphism in miR-27a rs895819 has been associated with breast cancer (BC) risk, but studies have reported inconsistent results. This meta-analysis investigated the possible association between miR-27a rs895819 polymorphism and BC risk.Methods:PubMed, EMBASE, Google Scholar, and the Chinese National Knowledge Infrastructure (CNKI) databases were systematically searched to identify relevant studies in English and Chinese. Meta-analyses were performed to examine the association between miR-27a rs895819 and BC susceptibility.Results:A total of 16 case–control studies involving 6118 cases and 7042 controls were included. Analysis using five genetic models suggested no significant association between miR-27a rs895819 polymorphism and BC risk in the total population, or specifically in Asian or Chinese subpopulations. In the Caucasian subpopulation, however, the G-allele and AG genotype at rs895819 were significantly associated with decreased BC risk according to the allelic model (OR 0.90, 95% CI 0.84–0.97, P = .004) and heterozygous model (OR 0.89, 95% CI 0.81–089, P = .02), while the wild-type AA genotype was significantly associated with increased BC risk according to the dominant model (OR 1.13, 95% CI 1.03–1.24, P = .007).Conclusion:These results indicate that among Caucasians, the wild-type AA genotype at rs895819 may confer increased susceptibility to BC, while the G-allele and AG genotype may be protective factors. These conclusions should be verified in large, well-designed studies.     

Value of Quantitative and Qualitative Analyses of Circulating Cell-Free DNA as Diagnostic Tools for Hepatocellular Carcinoma: A Meta-Analysis

Qualitative and quantitative analyses of circulating cell-free DNA (cfDNA) are potential methods for the detection of hepatocellular carcinoma (HCC). Many studies have evaluated these approaches, but the results have been variable. This meta-analysis is the first to synthesize these published results and evaluate the use of circulating cfDNA values for HCC diagnosis.All articles that met our inclusion criteria were assessed using QUADAS guidelines after the literature research. We also investigated 3 subgroups in this meta-analysis: qualitative analysis of abnormal concentrations of circulating cfDNA; qualitative analysis of single-gene methylation alterations; and multiple analyses combined with alpha-fetoprotein (AFP). Statistical analyses were performed using the software Stata 12.0. We synthesized these published results and calculated accuracy measures (pooled sensitivity and specificity, positive/negative likelihood ratios [PLRs/NLRs], diagnostic odds ratios [DORs], and corresponding 95% confidence intervals [95% CIs]). Data were pooled using bivariate generalized linear mixed model. Furthermore, summary receiver operating characteristic curves and area under the curve (AUC) were used to summarize overall test performance. Heterogeneity and publication bias were also examined.A total of 2424 subjects included 1280 HCC patients in 22 studies were recruited in this meta-analysis. Pooled sensitivity and specificity, PLR, NLR, DOR, AUC, and CIs of quantitative analysis were 0.741 (95% CI: 0.610–0.840), 0.851 (95% CI: 0.718–0.927), 4.970 (95% CI: 2.694–9.169), 0.304 (95% CI: 0.205–0.451), 16.347 (95% CI: 8.250–32.388), and 0.86 (95% CI: 0.83–0.89), respectively. For qualitative analysis, the values were 0.538 (95% CI: 0.401–0.669), 0.944 (95% CI: 0.889–0.972), 9.545 (95% CI: 5.298–17.196), 0.490 (95% CI: 0.372–0.646), 19.491 (95% CI: 10.458–36.329), and 0.87 (95% CI: 0.84–0.90), respectively. After combining with AFP assay, the values were 0.818 (95% CI: 0.676–0.906), 0.960 (95% CI: 0.873–0.988), 20.195 (95% CI: 5.973–68.282), 0.190 (95% CI: 0.100–0.359), 106.270 (95% CI: 22.317–506.055), and 0.96 (95% CI: 0.94–0.97), respectively.The results in this meta-analysis suggest that circulating cfDNA have potential value for HCC diagnosis. However, it would not be recommended for using independently, which is based on the nonrobust results. After combining with AFP, the diagnostic performance will be improved. Further investigation with more data is needed.     

A Comprehensive Meta-Analysis of MicroRNAs for Predicting Colorectal Cancer

Colorectal cancer (CRC) has been defined as a common malignancy due to its prevailing incidence in both males and females. Recently, the intrinsic value of microRNAs (miRNAs) with respect to early cancer diagnosis has been contentious as the diagnostic accuracy of miRNAs significantly varied across different studies. As a result of this, this pioneer meta-analysis was proposed to address this issue.Qualified studies were obtained through electronic systematical searching in Medline, Embase, and PubMed. On the basis of the random-effects model, we calculated the pooled sensitivity (SEN), specificity (SPE), and area under the receiver operating characteristics curve (AUC) to assess the diagnostic accuracy of miRNAs. Subgroup analysis and meta-regression were implemented to determine how different confounding factors affect the overall diagnostic accuracy which were considered important sources of heterogeneity. All the statistical analyses were conducted with R 3.2.1 software.We incorporated 103 studies from 36 articles with a total of 3124 CRC patients and 2579 healthy individuals. MiRNAs have a good performance with the following pooled estimates: SEN = 0.769 (95% CI = 0.733–0.802), SPE = 0.806 (95% CI = 0.781–0.829), AUC = 0.857, and partial AUC = 0.773. As suggested by subgroup analyses and meta-regression, multiple miRNAs appeared to be more favorable than single miRNA (AUC: 0.918 > 0.813, partial AUC: 0.848 > 0.701, sensitivity = 0.853 > 0.718, specificity = 0.860 > 0.772). Compared with samples of plasma, blood, tissue, and feces, miRNA obtained from serum samples were more powerful for detecting CRC particularly in Asian.Our study provided exclusive evidence that multiple miRNAs extracted from serum samples had superior diagnostic performance over single miRNA for screening CRC. Therefore, this approach that is characterized by high specificity and noninvasive nature may assist in early diagnosis of CRC particularly in Asian.     

Diagnostic accuracy of electronic surveillance tool for catheter-associated urinary tract infections in tertiary care hospitals: A meta-analysis

Background:Automated systems have been developed to reduce labor-intensive manual recordings during nosocomial infection surveillance. The diagnostic accuracies of these systems have differed in various settings.Methods:We designed this meta-analysis to evaluate the diagnostic accuracy of an electronic surveillance tool for catheter-associated urinary tract infections (CAUTIs) in tertiary care hospitals. We systematically searched databases such as Medline, Scopus, Cochrane library and Embase (from inception until November 2019) for relevant studies. We assessed the quality of trials using the diagnostic accuracy studies-2 tool, and performed a meta-analysis to obtain a pooled sensitivity and specificity for electronic surveillance. We included 6 studies with 16,492 patients in the analysis.Results:We found a pooled sensitivity of electronic diagnostic surveillance for CAUTIs of 97.5% (95% confidence interval [CI], 67.6–99.9%) and a pooled specificity of 92.6% (95% CI, 55.2–99.2%). The diagnostic odds ratio was 494 (95% CI, 89–2747). The positive likelihood ratio was 13.1 (95% CI, 1.63–105.8) and the negative likelihood ratio 0.02 (95% CI, 0.001–0.40). A bivariate box plot indicated the possibility of heterogeneity between the included studies.Conclusion:Our review suggests that electronic surveillance is useful for diagnosing CAUTIs among hospitalized patients in tertiary care hospitals due to its high sensitivity and specificity.     

Diagnostic and Prognostic Value of Serum Interleukin-6 in Colorectal Cancer

The application of serum interleukin-6 (IL-6) in the diagnosis and prognosis of colorectal cancer (CRC) has been evaluated in many studies, whereas the results were contradictive.The aim of this study was to systematically evaluate this issue.An original study was conducted to explore the diagnostic value of serum IL-6 in CRC. Pubmed, Embase, and Cochrane library databases were searched for eligible studies.For diagnostic meta-analysis, aggregate data (AD) and individual participant data (IPD) meta-analyses were both adopted. The sensitivity and specificity were pooled and a summary receiver-operating characteristic (ROC) curve was constructed. For prognostic meta-analysis, study-specific hazard ratios (HRs) of IL-6 for survival were summarized. Secondary analysis of survival data was performed to synthesize the Kaplan–Meier curves.Total 17 studies (including our study) were included in this meta-analysis. The pooled sensitivity, specificity, and area under curve (AUC) of serum IL-6 were 0.72 (95% CI: 0.46–0.88), 0.74 (95% CI: 0.56–0.86), and 0.79 (95% CI: 0.75–0.82) in CRC diagnosis, respectively. Further, IPD meta-analysis strengthened the diagnostic value of serum IL-6 (the AUC, sensitivity, and specificity were 0.794, 0.606, and 0.839, respectively). For prognostic analysis, the high serum level of IL-6 was inversely associated with overall survival (OS) (pooled HR = 1.76, 95% CI: 1.42–2.19, P < 0.001) and disease-free survival (DFS) (pooled HR = 2.97, 95% CI: 1.76–5.01, P < 0.001). The synthesized Kaplan–Meier curves indicated that CRC patients with higher serum IL-6 level had a worse OS (P = 0.0027) and DFS (P < 0.001), which further support the prognostic value of serum IL-6 in CRC patients.The present study confirmed that serum IL-6 may be a potential biomarker for CRC diagnosis, and the high serum IL-6 level was associated with poor prognosis for both CRC overall survival and disease-free survival.The study has been registered in an international registry of systematic reviews PROSPERO (CRD42013006485).     

Comparison of the Wells score with the revised Geneva score for assessing suspected pulmonary embolism: a systematic review and meta-analysis

The Wells score and the revised Geneva score are two most commonly used clinical rules for excluding pulmonary embolism (PE). In this study, we aimed to assess the diagnostic accuracy of these two rules; we also compared the diagnostic accuracy between them. We searched PubMed and Web of science up to April 2015. Studies assessed Wells score and revised Geneva score for diagnosis suspected PE were included. The summary area under the curve (AUC) and the 95 % confidence interval (CI) were calculated. Eleven studies were included in this meta-analysis. For Wells score, the sensitivity ranged from 63.8 to 79.3 %, and the specificity ranged from 48.8 to 90.0 %. The overall weighted AUC was 0.778 (95 % CI 0.740–0.818; Z = 9.88, P < 0.001). For revised Geneva score, the sensitivity ranged from 55.3 to 73.6 %. The overall weighted AUC was 0.693 (95 % CI 0.653–0.736; Z = 11.96, P < 0.001). 95 % CIs of two AUCs were not overlapped, which indicated Wells score was more accurate than revised Geneva score for predicting PE in suspected patients. Meta-regression showed diagnostic accuracy of these two rules was not related with PE prevalence. Sensitivity analysis by only included prospective studies showed the results were robust. Our results showed the Wells score was more effective than the revised Geneva score in discriminate PE in suspected patients.     

The diagnostic value of interleukin 6 as a biomarker for gastric cancer: A meta-analysis and systematic review

Background:Gastric cancer is one of the most common cancers and a main cause of global cancer death. The expression of interleukin 6 is associated with the risk of gastric cancer. But the diagnostic accuracy of interleukin 6 remains unclear. This study was designed to assess the diagnostic performance of interleukin 6 in gastric cancer diagnosis.Methods:The related data was obtained from Oncomine and studied using bioinformatics analysis. The PubMed, Embase, Cochrane Library, Web of science databases were searched for related studies published from inception to July 14, 2020. Measuring tools of diagnostic performance including sensitivity, specificity, and diagnostic odds ratio were pooled using bivariate mixed-effects meta-analysis model. The summery receiver operator characteristic curves were plotted.Results:The result from Oncomine showed that the expression of interleukin 6 in gastric cancer (GC) patients was higher than the normal groups (P < .05). Furthermore, a total of 4 eligible articles were enrolled, containing 390 cases and 404 controls. The diagnostic results were as follows: a sensitivity of 0.80 (95% confidence interval [CI] 0.57–0.92), a specificity of 0.86 (95% CI 0.74–0.93), a positive likelihood ratio of 5.76 (95% CI 3.49–9.49), a negative likelihood ratio of 0.23 (95% CI 0.11–0.51) and a diagnostic odds ratio of 24.58 (95% CI 14.14–42.73). The summary area under the receiver operating characteristic curves was 0.90 (95% CI 0.87–0.93).Conclusion:Higher interleukin 6 expression was detected in GC patients, and interleukin 6 could be a helpful indicator of diagnosis of gastric cancer. Further large-scale prospective studies are required for identifying the diagnostic value of interleukin 6 in gastric cancer.     

Diagnostic Value of Presepsin for Sepsis: A Systematic Review and Meta-Analysis

Several individual studies have reported the diagnostic accuracy of presepsin (sCD14-ST) for sepsis, but the results are inconsistent.The present systematic review and meta-analysis pooled data to better ascertain the value of circulatory presepsin as a biomarker for sepsis.Studies published in English before November 7, 2014 and assessing the diagnostic accuracy of presepsin for sepsis were retrieved from medical databases.The quality of eligible studies was assessed using a revised Quality Assessment for Studies of Diagnostic Accuracy (QUADAS-2). The overall diagnostic accuracy of presepsin for sepsis was pooled according to a bivariate model. Publication bias was assessed using Deek funnel plot asymmetry test.Eleven studies satisfied the inclusion criteria. The overall diagnostic sensitivity of presepsin for sepsis was 0.83 (95% CI: 0.77–0.88), and specificity was 0.78 (95% CI: 0.72–0.83). The area under the summary receiver operating characteristic curve was 0.88 (95% CI: 0.84–0.90). The pretest probability of sepsis was 0.56 among all subjects. When presepsin was introduced as the diagnostic test for sepsis, the posttest probabilities were 0.81 for a positive result and 0.19 for a negative. The major design deficits of the included studies were lack of prespecified thresholds and patient selection bias. The publication bias was negative.Presepsin is an effective adjunct biomarker for the diagnosis of sepsis, but is insufficient to detect or rule out sepsis when used alone.     

Diagnostic value of microRNA-148/152 family in non-small-cell lung cancer (NSCLC): A systematic review and meta-analysis

Backgrounds:Non-small-cell lung cancer (NSCLC) is the most common type of lung cancer with extremely high morbidity and mortality.Objective:To evaluate the diagnostic value of the blood miR-148/152 family to NSCLC by meta-analysis.Methods:PubMed, Embase (via Ovid), The Cochrane Library, web of science, and Chinese National Knowledge Infrastructure were retrieved using miR-148, miR-152, and NSCLC as search terms for studies about miR-148/152 family in the diagnosis of NSCLC, the quality assessment of diagnostic accuracy studies was adopted to evaluate the quality of literature, STATA 12.0 and Meta-Disc 1.4 were used to conduct meta-analysis and to probe the clinical utility (with plotting the Fagan Nomogram).Results:A total 2145 cases in 8 trials published in 4 studies finally enrolled for final analysis. The area under the curve of the summary receiver operating characteristic was 0.87 [0.83–0.89], the pooled sensitivity was 0.79 [0.74, 0.83], the pooled specificity was 0.81 [0.76, 0.85] and the diagnosis odds ratio was 15.53 [10.88–22.17], the integrated positive likelihood ratio was 4.1 [3.30, 5.20] and the integrated negative likelihood ratio was 0.27 [0.22, 0.33].Conclusion:Current evidence indicated that miR-148/152 family might be served as novel non-invasive diagnostic biomarkers for NSCLC diagnosis with good sensitivity and specificity. it still needs more research with high quality, large sample sizes, and multiple centers for further verification.