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.     

Diagnostic significance of circulating miRNAs in Kawasaki disease in China: Current evidence based on a meta-analysis

Background:There is no golden standard for the diagnosis of Kawasaki disease (KD), the most common cause of acquired heart disease in children in many countries. In recent years, many studies have focused on the relationship between microRNAs (miRNAs) and KD. Thus, we perform this meta-analysis to understand the role of circulating miRNAs as a biomarker to detect KD.Methods:We searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials, and China National Knowledge Infrastructure through March 10, 2019. Meta-disc 1.4 and STATA 15.1 (Stata Corporation, College Station, TX) were used to conduct the meta-analysis.Results:Six eligible articles were included in this meta-analysis. The overall performance of total mixed miRNAs detection was: pooled sensitivity, 0.7 (95% confidence interval, 0.66–0.74); pooled specificity, 0.87 (95% confidence interval, 0.83–0.90); and area under the summary receiver operating characteristic curves value (SROC), 0.8302. The meta-regression analysis indicated that the specimen types, the composition of the control group, and types of the reference miRNA were not responsible for the existing heterogeneities. The subgroup analysis showed that SROC of the plasma group (0.8890) was more significant than the serum group (0.7204), and SROC of the non-healthy control group (0.9622) was more significant than the healthy control group (0.8096).Conclusions: This is the first meta-analysis show that miRNAs may be used as novel biomarkers for detecting KD, especially for distinguishing KD from other febrile diseases. More studies are needed in the future to clarify the association between KD and miRNAs.PROSPERO registration number:CRD42019129976     

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.     

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.     

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.     

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.     

Appraising MicroRNA-155 as a Noninvasive Diagnostic Biomarker for Cancer Detection: A Meta-Analysis

Cancer has been a major public health issue all over the world and cancer patients diagnosed at early stages have a comparatively favorable prognosis. The association between specific dysregulated expressed microRNA-155 (miRNA-155, miR-155) and tumorigenesis has been identified by numerous studies. However, perplexity and inconsistence arise from a wide range of studies due to heterogeneity. Therefore, this meta-analysis was carried out to validate the association between miR-155 and tumorigenesis together with the clinical applicability of miR-155.Relevant studies were searched, identified, and selected from PubMed, Embase, Cochrane, Sinomed, and Wanfang database until July 5, 2015. Then, the sensitivity, specificity, and area under the summary receiver operator characteristic curve (AUC) were calculated to assess the overall performance miR-155 for cancer detection.A total of 25 studies were included in the meta-analysis with a total number of 1896 cancer patients and 1226 healthy controls. The overall sensitivity and specificity was 76.8% (95%CI: 71.1–81.7%) and 82.9% (95% CI: 77.5–87.3%), respectively. In addition, the pooled AUC and partial AUC was 0.867 and 0.718, respectively. Results from subgroup analyses suggested that the diagnostic accuracy of miR-155 in the Caucasian group was significantly higher than that in the Asian group. Similarly, serum sample type may provide better diagnostic value of miR-155 than plasma. Apart from that, miR-155 in breast cancer achieved the highest accuracy compared with miR-155 in other types of cancer.Results from meta-analysis suggested that miR-155 had great potential as a novel noninvasive biomarker for human cancer detection, particularly when breast cancer or Caucasian is involved. However, well-designed cohort or case control studies with large sample size should be implemented to confirm the diagnostic value of miR-155.     

Detection of gestational diabetes mellitus by circulating plasma and serum microRNAs: A systematic review and meta-analysis

Background and aimsThe diagnostic performance of microRNAs (miRNAs), which have recently emerged as a potential early diagnostic tool capable of detecting gestational diabetes mellitus (GDM) in its early stages, has yet to be systematically investigated. This meta-analysis aims to investigate the diagnostic utility of circulating plasma or serum miRNAs in detecting GDM patients.MethodsEligible studies were included and assessed for risk of bias with the Quality Assessment of Diagnostic Accuracy Studies 2 tool. A bivariate meta-analysis using the hierarchical summary receiver operating characteristic model was performed to estimate the pooled diagnostic value of miRNAs.ResultsTwelve studies (32 index tests) cumulating a total of 1768 patients were included in the present study. The pooled sensitivity of miRNAs was 74.5% (95% confidence interval [CI]: 63.7–82.9) and the pooled specificity was 84.1% (95% CI: 76.8–89.3). The overall area under the curve was 0.869 (95% CI: 0.818–0.907) with a relatively narrow 95% confidence region and a wide 95% prediction region.ConclusionmiRNAs may emerge as a promising diagnostic tool in detecting GDM. Further cross-sectional cohort studies with larger sample sizes and more heterogeneous populations, and studies evaluating the accuracy of multiple miRNAs in diagnosing GDM are required to confirm our findings.     

A panel of circulating miRNAs as diagnostic biomarkers for screening multiple myeloma: a systematic review and meta‐analysis

Circulating microRNAs (miRNAs) have been proved to be effective diagnostic markers for multiple myeloma (MM). The meta‐analysis was aimed to evaluate the diagnostic value of related miRNAs. Multiple databases (PubMed, Web of Science, EMBASE, Cochrane Library, CBM, and CNKI) were systematically searched for available studies up to March 2016. All data were analyzed with the help of software revman 5.3 and metadisc 1.4. The eligible articles’ quality was estimated by QUADAS‐2, and pooled parameters were acquired with the bivariate random‐effects meta‐analysis model. Subgroup analysis and meta‐regression were conducted to explore the heterogeneity of studies included. After steps of screening, seven qualified literatures were selected. They consisted of 22 studies that included 486 newly diagnosed MM patients and 292 healthy controls. Summary receiver operating characteristic (SROC) analyses of all miRNAs showed an area under the curve (AUC) of 0.86 (95%CI, 0.82–0.91). Together with the AUC, the positive likelihood ratio‐PLR 4.45 (95%CI, 3.28–6.04), negative likelihood ratio‐NLR 0.29 (95%CI, 0.24–0.35), and diagnostic odds ratio‐DOR 17.59 (95%CI, 11.26–27.4) confirmed that circulating miRNAs possessed relatively high diagnostic value in discriminating MM patients from healthy controls. For miRNAs combined together, miRNA‐1308/miRNA‐720 had the highest sensitivity 0.96 (95%CI, 0.79–1.00) and specificity 0.92 (95%CI 0.64–1.0). The subgroup and meta‐regression analyses also showed that miRNAs profiling was the sole source of heterogeneity, and the diagnostic accuracy of combined miRNAs was 6.02 times higher than single one. Combined circulating miRNAs in serum or plasma may be highly effective biomarker for diagnosis of MM.     

Prognostic value of aldo-keto reductase family 1 member B10 (AKR1B10) in digestive system cancers: A meta-analysis

Background:Numbers of studies have reported that the expression of aldo-keto reductase family 1 member B10 (AKR1B10) is abnormal in digestive system cancers, and could be used as a prognostic biomarker. However, the results are argued. Therefore, we conduct a meta-analysis to comprehensively evaluate the prognostic value of high AKR1B10 expression for overall survival (OS), disease specific survival (DSS), and disease-free survival/recurrence-free survival (DFS/PFS) in digestive system cancers.Methods:Hazard ratios (HRs) with its 95% confidence intervals (CIs) were calculated to assess the prognostic value of AKR1B10 by using the random effects model. The STATA version 12.0 software were used to perform all the analyses.Results:Eleven articles including 1428 patients involved in this meta-analysis. The pooled analysis suggested that high AKR1B10 expression was not associated with OS (HR: 1.18; 95% CI: 0.69–2.00) and DFS/PFS (HR: 1.08, 95% CI: 0.67–1.76) in digestive system cancers. However, Further analysis revealed that high AKR1B10 expression indicated poor OS in oral squamous cell carcinomas (OSCC) (HR: 2.92, 95% CI: 1.86–4.58) and favorable DSS in hepatocellular carcinoma (HCC) (HR: 0.71, 95% CI: 0.52–0.97).Conclusions:The prognostic value of high AKR1B10 expression varied in different types of digestive system cancers. Further studies exploring the prognostic role of AKR1B10 in digestive system cancers are needed.     

呼出气一氧化氮对慢性咳嗽人群中咳嗽变异型哮喘的诊断价值:Meta分析

目的 咳嗽变异型哮喘(cough variant asthma,CVA)是慢性咳嗽的常见病因.本研究旨在应用Meta分析的方法评价呼出气一氧化氮(fractional exhaled nitric oxide,FeNO)检测对慢性咳嗽人群CVA诊断的有效性和准确性.方法 检索Embase、PubMed、Medline、Cochrane library、Web of science、百度学术、中国期刊网和万方数据库,全面收集FeNO在慢性咳嗽人群对CVA诊断的文献,检索时限均从建库至2016年8月.根据QUADAS-2量表的评价标准对文献进行质量评价.用Stata 14.0、RevMan 5.0软件对文献进行异质性分析,并计算合并的敏感性、特异性、阳性似然比、阴性似然比、诊断优势比和SROC曲线下面积.结果 共纳入文献5篇,涉及慢性咳嗽患者704例.FeNO检测诊断CVA合并的敏感度、特异度、阳性似然比、阴性似然比、诊断优势比、SROC曲线下面积分别为0.74 [95％可信区间(CI):0.69～0.79],0.85 (95％ CI:0.81～0.88),4.73 (95％CI:3.70～6.05),0.31 (95％ CI:0.26～0.38),14.84 (95％CI:10.11～21.79)和0.87 (95％CI:0.84～0.89).结论 FeNO对慢性咳嗽人群中CVA的诊断有较好的敏感度和特异度,可作为重要的诊断指标.     

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).     

The diagnostic value of confocal laser endomicroscopy for gastric cancer and precancerous lesions among Asian population: a system review and meta-analysis

Objective: The objective of this study is to evaluate the diagnostic value of confocal laser endomicroscopy (CLE) in detection of gastric cancer (GC), gastric intraepithelial metaplasia (GIM), and gastric intraepithelial neoplasia (GIN) lesions.

Method: PubMed, the Cochrane Library, and Wangfang databases were searched to include eligible articles about CLE in detection of gastric lesions. After study selection, quality assessment and data extraction conducted by two reviewers independently, meta-analysis was performed by Meta-Disc 1.4. The pooled sensitivity and specificity was calculated, receiver operating characteristic (ROC) curve was constructed, and the area under ROC curve (AUC) was calculated.

Results: Twenty-three studies evaluating the diagnostic value of CLE were included. For the diagnosis of GC lesions, the pooled sensitivity, specificity, and AUC were 91% (88–94%), 99% (99–99%), and 0.9513, respectively. For the diagnosis of lesions, the pooled sensitivity, specificity, and AUC were 92% (90–94%), 97% (96–98%), and 0.9774, respectively. For the diagnosis of GIN lesions, the pooled sensitivity, specificity and AUC were 81% (75–85%), 98% (97–98%), and 0.9204, respectively.

Conclusions: CLE can provide an accurate diagnosis with high sensitivity and specificity for GC, GIM, and GIN lesions. The results should be confirmed by well-designed, multi-centered, randomized controlled, and double blinded trials with large samples.     

AFP-L3 for the diagnosis of early hepatocellular carcinoma: A meta-analysis

Background:The present study aimed to systematically evaluate the diagnostic value of an isoform of alpha-fetoprotein (AFP), AFP-L3, for early hepatocellular carcinoma (HCC) by a meta-analysis.Methods:Diagnostic reports of AFP-L3% in early HCC were searched in the PubMed, Web of Science, Cochrane Library, and Embase databases up to December 2019. The retrieved literature was reviewed, and eligible articles were selected. Data were extracted from the eligible articles, and the risk of bias was evaluated according to the Quality Assessment of Diagnostic Accuracy Studies scale. Statistical analyses were conducted by MetaDiSc1.4 and RevMan5.3 software. The sensitivities, specificities, and diagnostic odds ratios were pooled. The summary receiver operating characteristic curve was drawn, and the area under the curve was calculated.Results:Six studies with acceptable quality were included in the meta-analysis involving 2447 patients. No threshold effect was observed among the 6 studies, but there was obvious heterogeneity. The pooled sensitivity, specificity, and positive and negative likelihood ratios of AFP-L3% for the diagnosis of early HCC were 0.34 (95% CI 0.30–0.39, P < .0001), 0.92 (95% CI 0.91–0.93, P < .0001), 4.46 (95% CI 2.94–6.77, P = .0033), and 0.71 (95% CI 0.61–0.82, P = .0004), respectively. The diagnostic odds ratio was 6.78 (95% CI 4.02–11.44, P = .0074). The the area under the curve of the summary receiver operating characteristic was 0.755 (95% CI 0.57–0.94).Conclusion:AFP-L3% has high specificity but low sensitivity for diagnose early HCC, suggesting that AFP-L3% is more valuable for excluding HCC in conditions with elevated AFP than for diagnosing early HCC. In addition, a hypersensitive detection method can improve the diagnostic accuracy of AFP-L3% for early HCC.     

Clinical use of microRNAs as potential non‐invasive biomarkers for detecting non‐small cell lung cancer: A meta‐analysis

Emerging studies have revealed that microRNA (miRNA) in body fluid may serve as a potential biomarker to detect non‐small cell lung cancer (NSCLC). However, the diagnostic accuracy of miRNA for NSCLC detection is still under debate because there is inconsistency in previous studies. Hence, we conducted this meta‐analysis to comprehensively evaluate the diagnostic performance of miRNA. A systematic literature search was performed to retrieve relevant articles in PubMed and other databases, and STATA 12.0 (StataCorp, College Station, TX, USA) was used to calculate the pooled parameters. A total of 28 articles involving 2121 NSCLC patients and 1582 healthy controls were included in this meta‐analysis. The overall pooled sensitivity and specificity of miRNA were 0.75 and 0.79, respectively. The pooled positive likelihood ratio was 3.6, negative likelihood ratio was 0.32 and diagnostic odds ratio was 12. The area under the curve (AUC) was 0.84. Subgroup and meta‐regression analyses established that miRNA assays were more accurate in Caucasian populations (AUC of 0.86, sensitivity of 0.79 and specificity of 0.82, respectively) than in Asian populations (AUC, sensitivity and specificity of 0.83, 0.72 and 0.80, respectively). In addition, the multiple miRNA assays (AUC of 0.89, sensitivity of 0.83 and specificity of 0.82, respectively) showed a higher accuracy than single miRNA assays (AUC, sensitivity and specificity of 0.81, 0.77 and 0.71, respectively) in NSCLC detection. Subgroup analyses based on specimen types suggested that blood‐based miRNA (AUC of 0.86, sensitivity of 0.78 and specificity of 0.80, respectively) may have a higher diagnostic accuracy as biomarkers than sputum‐based miRNA (AUC of 0.81, sensitivity of 0.69 and specificity of 0.80, respectively). In conclusion, miRNA may serve as a potential biomarker in NSCLS detection, especially the multiple miRNA from blood, with a relatively high diagnostic accuracy.     

Utility of PET/CT in the Diagnosis and Staging of Extranodal Natural Killer/T-Cell Lymphoma: A Systematic Review and Meta-Analysis

The role of ¹⁸F-fuorodexoyglucose-positron emission tomography/computed tomography (¹⁸F-FDG-PET/CT) in the staging of Hodgkin lymphoma (HL) and aggressive B-cell non-Hodgkin lymphomas (NHL) has been demonstrated extensively. Nevertheless, the role of PET/CT in the diagnosis, staging, prognosis, and treatment evaluation of natural killer (NK)/T-cell lymphoma remains indeterminate.To systematically review and meta-analyze the publications on the value of ¹⁸F-FDG-PET/CT in the diagnosis and staging of NK/T-cell lymphoma.Pubmed, Embase, Cochrane Library, and some other database were searched for initial studies (last updated on May 8th, 2014).The eligibility criteria were studies assessing the usefulness of PET/CT in the staging of NK/T-cell lymphoma, patients were diagnosed as NK/T-cell lymphoma through pathology, or clinical and imaging follow-up.Sensitivities and specificities of ¹⁸F-FDG-PET/CT in individual studies were assessed. The summary receiver operating characteristic curve (sROC) and the area under the curve (AUC) were calculated. The “Meta-Disc 1.4” software was used for data analysis.Eight studies, with a total of 135 NK/T-cell lymphoma patients, were included in this meta-analysis. In terms of the 6 studies with patient based data, the pooled sensitivity and specificity of PET/CT in the diagnosis of NK/T-cell lymphoma were 0.95 (95% CI: 0.89–0.98) and 0.40 (95% CI: 0.09–0.78), respectively. For lesion-based analysis, with 1546 lesions included, the pooled sensitivity and specificity of PET/CT in the staging of NK/T-cell lymphoma were 0.98 (95% CI: 0.96–0.99) and 0.99 (95% CI: 0.99–1.00), respectively. For the patient based data, the AUC and ^∗Q index were 0.8537 and 0.7847, respectively. For lesion based data, the AUC and ^∗Q index were 0.9959 and 0.9755, respectively.The results of this current meta-analysis indicated that PET/CT could be used as a valuable diagnostic and staging tool for NK/T-cell lymphoma.     

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 accuracy of novel folate receptor-mediated staining solution detection (FRD) for CIN2+: A systematic review and meta analysis

Background:Early detection and diagnosis of high-grade cervical intraepithelial neoplasia grade 2 or higher (CIN2+) is critical for a good prognosis and appropriate treatment. The chief aim of our study was to evaluate the diagnostic performance of folate receptor-mediated staining solution detection (FRD) for CIN2+.Methods:We conducted a systematic review and meta-analysis by searching the PubMed and EMBASE databases for studies published until May 2020, which assessed the diagnostic accuracy of FRD, human papilloma virus (HPV) testing, and ThinPrep cytology test (TCT) for the detection of CIN2+. Bivariate models were used to compare the diagnostic performance of FRD, HPV, and TCT.Results:Six studies involving 2817 patients were included in this meta-analysis. The pooled specificity of FRD was higher than that of HPV and TCT for detecting CIN2+ (0.65, 0.12, and 0.39, respectively). The summary area under the receiver operating characteristic curve values using FRD, HPV, and TCT for detecting CIN2+ were 0.79, 0.95, and 0.77, respectively, indicating that FRD was superior to TCT. The diagnostic odds ratios of FRD, HPV, and TCT were 6 (95% CI: 5–7), 3 (95% CI: 2–5), and 3 (95% CI: 2–4), respectively, demonstrating that FRD had good diagnostic accuracy.Conclusion:FRD showed good diagnostic accuracy and higher specificity than HPV and TCT for detecting CIN2+. Based on our results, we propose that FRD could be a candidate for cervical screening, especially in underdeveloped countries.     

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.     

血清半乳甘露聚糖检测诊断侵袭性曲霉病价值的荟萃分析

目的 评价ELISA法检测血清半乳甘露聚糖(GM)诊断侵袭性曲霉病(IA)的价值.方法 检索Medline生物医学数据库、医学文摘资料库(EMbase)、OVID全文期刊库、中国生物医学文献数据库、中国生物医学期刊文献数据库及万方数据库等,检索时间为1991年1月至2008年12月,收集关于GM试验诊断IA临床价值的相关文献,进行质量评价、异质性分析、合并效应量、绘制合并受试者工作特征曲线并进行亚组分析.结果 纳入文献36篇,包括4959例患者,总体研究人群的IA平均患病率为11%(532/4959).荟萃分析结果显示,各研究间存在中等度异质性(I2=48.6%,P＜0.01),合并诊断优势比为19.10(95%CI为12.67～28.79),合并敏感度为0.66(95%CI为0.61～0.70),合并特异度为0.90(95%CI为0.89～0.90),阳性似然比为5.48(95%CI为4.27～7.02),阴性似然比0.38(95%CI为0.29～0.50),合并受试者工作特征曲线下面积为0.89.GM试验诊断IA的漏诊率为34%(168/490),误诊率为10%(466/4469);当采用的诊断临界值升高时敏感度下降,特异度升高;2次连续GM试验阳性较单次阳性诊断IA的敏感度降低,但特异度升高;年龄对GM试验诊断IA的效力无明显影响(P＞0.05);预防性抗真菌治疗或抗真菌治疗对GM试验诊断IA的敏感度和特异度均无明显影响(P＞0.05).结论 现有文献的荟萃分析结果表明,在高危人群中ELISA法检测GM抗原诊断IA具有较高价值.