Circulating miRNAs as Auxiliary Diagnostic Biomarkers for Multiple Myeloma: A Systematic Review, Meta-Analysis, and Recommendations

Multiple myeloma (MM) is a hematologic malignancy characterized by aberrant expansion of monoclonal plasma cells with high mortality and severe complications due to the lack of early diagnosis and timely treatment. Circulating miRNAs have shown potential in the diagnosis of MM with inconsistent results, which remains to be fully assessed. Here we updated a meta-analysis with relative studies and essays published in English before Jan 31, 2021. After steps of screening, 32 studies from 11 articles that included a total of 627 MM patients and 314 healthy controls were collected. All data were analyzed by REVMAN 5.3 and Stata MP 16, and the quality of included literatures was estimated by Diagnostic Accuracy Study 2 (QUADAS-2). The pooled area under the curve (AUC) shown in summary receiver operating characteristic (SROC) analyses of circulating miRNAs was 0.87 (95%CI, 0.81–0.89), and the sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were 0.79, 0.86, 5, 0.27, 22, respectively. Meta-regression and subgroup analysis exhibited that “miRNA cluster”, patient “detailed stage or Ig isotype” accounted for a considerable proportion of heterogeneity, revealing the importance of study design and patient inclusion in diagnostic trials; thus standardized recommendations were proposed for further studies. In addition, the performance of the circulating miRNAs included in MM prognosis and treatment response prediction was summarized, indicating that they could serve as valuable biomarkers, which would expand their clinical application greatly.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=234297, PROSPERO, identifier (CRD42021234297).

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Predictive value of pregnancy-associated plasma protein-A in relation to fetal loss: A systematic review and meta-analysis

International Journal of Reproductive BioMedicine ◽

10.18502/ijrm.v13i6.7281 ◽

2020 ◽

Author(s):

Zahra Hadizadeh-Talasaz ◽

Ali Taghipour ◽

Seyede Houra Mousavi-Vahed ◽

Robab Latifnejad Roudsari

Keyword(s):

Systematic Review ◽

Likelihood Ratio ◽

Plasma Protein ◽

Predictive Value ◽

Meta Analysis ◽

Protein A ◽

Fetal Loss ◽

Positive Likelihood Ratio ◽

Negative Likelihood Ratio ◽

Forest Plot

Background: For a woman with bleeding and threatened abortion, ultrasound scan is done to confirm the viability of the fetus; however, 10-15% of the embryos are eventually aborted. Distinguishing between women with good and poor prognosis can be a helpful approach. Objective: This study aimed to review the predictive value of Pregnancy-associated Plasma Protein A (PAPP-A) in relation to the diagnosis of fetal loss. Materials and Methods: The articles published in multiple databases including Web of Science, PubMed, MEDLINE, Scopus, and Persian databases such as ISC, Magiran, and IranMedx were searched for articles published until May 2019. MeSH terms was used for searching the databases including fetal loss OR pregnancy loss OR abortion OR miscarriage with the following word using AND; Pregnancy-Associated Plasma Protein- A OR PAPP-A. Two reviewers extracted data and recorded them in a pre-defined form and assessed the quality of articles using the Newcastle-Ottawa tool. Meta-analysis was done using the Comprehensive Meta-Analysis/2.0 software and MetaDisc. Results: A total number of 16 studies were eligible for the qualitative data synthesis, out of which 8 studies were included in the meta-analysis. All studies had high and medium quality. The forest plot analysis showed a sensitivity of 57% (95% CI: 53-63%), a specificity of 83% (95% CI: 80-85%), a positive likelihood ratio of 3.52 (95% CI: 2.44- 5.07), a negative likelihood ratio of 0.54 (95% CI: 0.37-0.79), and a diagnostic odds ratio of 6.95 (95% CI: 3.58-13.50). Conclusion: PAPP-A cannot be recommended on a routine basis for predicting fetal loss and still further research with a combination of other biomarkers is required. Key words: Pregnancy-associated plasma protein-A, Fetal loss, Pregnancy, Systematic review.

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Prognostic Value of N-terminal Probrain Natriuretic Peptide for Patients with Acute Respiratory Distress Syndrome: A Systematic Review and Meta-Analysis

BioMed Research International ◽

10.1155/2020/3472615 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Qi Ni ◽

Chaoqian Li ◽

Hua Lin

Keyword(s):

Systematic Review ◽

Acute Respiratory Distress Syndrome ◽

Likelihood Ratio ◽

Odds Ratio ◽

Distress Syndrome ◽

Meta Analysis ◽

Positive Likelihood Ratio ◽

Negative Likelihood Ratio ◽

Diagnostic Odds Ratio ◽

Sensitivity Specificity

Objectives. The mortality rate of patients with acute respiratory distress syndrome (ARDS) is high. Hence, it is crucial to identify a reliable biomarker with wide clinical applications for predicting the prognosis of patients with ARDS. This systematic review and meta-analysis was conducted to investigate the value of plasma N-terminal probrain natriuretic peptide (NT-proBNP) for predicting mortality in patients with ARDS. Methods. An electronic search of databases including PubMed, Web of Science, Cochrane Library, and Chinese National Knowledge Infrastructure was conducted up to May 31, 2019, without language restrictions. The quality of the included studies was evaluated using QUADAS-2. Data were extracted and analyzed to obtain pooled estimates of sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio. A forest graph was used to evaluate heterogeneity. Potential causes of heterogeneity were further explored by subgroup analysis based on the testing day, testing method, observation endpoint, or cut-off points. A summary receiver operating characteristic curve was drawn to obtain the pooled area under the curve. Results. A total of 7 studies involving 581 patients with ARDS were included. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were as follows: 0.79 (95% CI: 0.72–0.84), 0.79 (95% CI: 0.66–0.88), 3.68 (95% CI: 2.16–6.28), 0.27 (95% CI: 0.20–0.38), and 13.58 (95% CI: 6.17–29.90), respectively. The results of subgroup analysis showed that the testing day influenced the summary sensitivity and that the cut-off points influenced the summary sensitivity and specificity. Conclusion. Our results indicate that elevated plasma NT-proBNP levels have a moderate value for predicting the mortality of patients with ARDS.

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The value of miR-155 as a biomarker for the diagnosis and prognosis of lung cancer: a systematic review with meta-analysis

10.21203/rs.2.9996/v2 ◽

2019 ◽

Author(s):

Chuchu Shao ◽

Fengming Yang ◽

Zhiqiang Qin ◽

Xinming Jing ◽

Yongqian Shu ◽

...

Keyword(s):

Lung Cancer ◽

Systematic Review ◽

Likelihood Ratio ◽

Meta Analysis ◽

Positive Likelihood Ratio ◽

Disease Free Survival ◽

Negative Likelihood Ratio ◽

Free Survival ◽

Diagnosis And Prognosis ◽

Potential Biomarker

Abstract Background: Recently, a growing number of studies have reported the coorelation between miR-155 and the diagnosis and prognosis of lung cancer, but results of these researches were still controversial due to insufficient sample size. Thus, we carried out the systematic review and meta-analysis to figure out whether miR-155 could be a screening tool in the detection and prognosis of lung cancer. Methods: A meta-analysis of 13 articles with 19 studies was performed by retrieving the PubMed, Embase and Web of Science. We screened all correlated literaters until December 1st, 2018. For the diagnosis analysis of miR-155 in lung cancer, sensitivity(SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and area under the ROC curve (AUC) were pooled to evaluate the accuracy of miRNA-155 in the diagnosis of lung cancer. For the prognosis analysis of miR-155 in lung cancer, the pooled HRs and 95% CIs of miR-155 for overall survival/disease free survival/progression-free survival (OS/DFS/PFS) were calculated. In addition, Subgroup and meta-regression analyses were performed to distinguish the potential sources of heterogeneity between studies. Results: For the diagnostic analysis of miR-155 in lung cancer, the pooled SEN and SPE were 0.82 (95% CI: 0.72-0.88) and 0.78 (95% CI: 0.71-0.84), respectively. Besides, the pooled PLR was 3.75 (95% CI: 2.76-5.10), NLR was 0.23 (95% CI: 0.15-0.37), DOR was 15.99 (95% CI: 8.11-31.52) and AUC was 0.87 (95% CI: 0.84-0.90), indicating a significant value of miR-155 in the lung cancer detection. For the prognostic analysis of miR-155 in lung cancer, up-regulated miRNA-155 expression was not significantly associated with a poor OS (pooled HR = 1.26, 95% CI: 0.66-2.40) or DFS/PFS (pooled HR = 1.28, 95% CI: 0.82-1.97). Conclusions: The present meta-analysis demonstrated that miR-155 could be a potential biomarker for the detection of lung cancer but not an effective biomarker for predicting the outcomes of lung cancer. Furthermore, more well-designed researches with larger cohorts were warranted to confirm the value of miR-155 for the diagnosis and prognosis of lung cancer.

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Blood-Based Circulating MicroRNAs are Potential Diagnostic Biomarkers for Leukemia: Result from a Meta-Analysis

Cellular Physiology and Biochemistry ◽

10.1159/000443046 ◽

2016 ◽

Vol 38 (3) ◽

pp. 939-949 ◽

Cited By ~ 8

Author(s):

Li-hua Xu ◽

Yang Guo ◽

Xue-Li Zhang ◽

Jia-jia Chen ◽

Shao-yan Hu

Keyword(s):

Diagnostic Accuracy ◽

Likelihood Ratio ◽

Meta Analysis ◽

Positive Likelihood Ratio ◽

Negative Likelihood Ratio ◽

Sensitivity Analyses ◽

Cochrane Library ◽

Circulating Mirnas ◽

Diagnostic Biomarkers ◽

Circulating Micrornas

Aims: Circulating microRNAs (miRNAs) as biomarkers for leukemia have been validated by emerging studies. This meta-analysis aims to estimate the overall diagnostic accuracy of blood-based circulating miRNAs for leukemia. Methods: We searched multiple databases (PubMed, EMBASE, Cochrane Library, CNKI, Wan Fang Data and CQVIP) up to June 18, 2015. Results: 32 studies from 10 publications were included in this meta-analysis. Diagnostic capacity was evaluated by pooled sensitivity, specifIcity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) through random-effects model. Sensitivity analyses were sequentially performed to find potential sources of heterogeneity. The quality of included studies was assessed by QUADAS (quality assessment for studies of diagnostic accuracy). Meta-Disc 1.4 and Stata 12.0 software were used to perform the meta-analysis. A high diagnostic accuracy was displayed, with a sensitivity of 0.84, a specificity of 0.88, a PLR of 7.20, a NLR of 0.18, a DOR of 52, and an AUC of 0.94. Subgroup analyses revealed better performance for combined miRNAs, acute myeloid leukemia patients and Asian population than other subgroups. Conclusion: Our analyses suggested that blood-based circulating miRNAs are promising diagnostic biomarkers for leukemia, especially combined miRNAs. Its clinical application awaits further study.

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Pentraxin 3 as a promising biomarker for cancer detection: a systematic review and meta-analysis

10.21203/rs.2.16075/v1 ◽

2019 ◽

Author(s):

Qindong Liang ◽

Guangjie Zhang ◽

Huaan Huang ◽

Nai Xing ◽

Shangchun Sheng ◽

...

Keyword(s):

Systematic Review ◽

Likelihood Ratio ◽

Cancer Detection ◽

Large Scale ◽

Meta Analysis ◽

Positive Likelihood Ratio ◽

Negative Likelihood Ratio ◽

Cochrane Library ◽

Pentraxin 3 ◽

Potential Biomarker

Abstract Background Mounting studies reported that circulating pentraxin 3 (PTX3) expression level was significantly different between cancer patients and healthy groups, suggesting that PTX3 may be a potential biomarker for cancer detection. However, the results were inconsistent. In this paper, a systematic review and meta-analysis was performed to quantitatively assess the diagnostic value of PTX3 in cancer detection.Methods A comprehensive computerized literature search was conducted in Embase, PubMed, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure (CNKI) from inception to July 31, 2019. Eligible studies were identified and raw data were extracted. Diagnostic estimates were synthesized using STATA (version 12.0) and MetaDisc (version 1.4) statistical software.Results Overall, 9 studies from 8 citations with a total of 1408 cancer patiens and 3116 controls were included in this meta-analysis. The global sensitivity was 0.70 (95% confidence interval (CI): 0.67 – 0.72), and the specificity was 0.77 (95% CI: 0.75 – 0.78). The pooled positive likelihood ratio (PLR), negative likelihood ratio (NLR), and the diagnostic odds ratio (DOR) were 2.86 (95% CI: 2.29 – 3.56), 0.40 (95% CI: 0.32 – 0.50) and 7.38 (95% CI: 5.05 – 10.78), respectively. The merged AUC was 0.80 (95% CI: 0.76 – 0.83).Conclusion The serum PTX3 appears to be a reliable biomarker for cancer detection though large-scale multicenter studies are needed.

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Diagnostic acuuracy of cerebrospinal fluid and serum-isolated exosomes for glioblastoma: a systematic review and meta-analysis

10.21203/rs.2.22976/v1 ◽

2020 ◽

Author(s):

Davod Jafari ◽

Amir Tiyuri ◽

Elmnaz Rezaei ◽

Yousef Moradi ◽

Rasool Jafari ◽

...

Keyword(s):

Systematic Review ◽

Early Detection ◽

Likelihood Ratio ◽

Meta Analysis ◽

Grey Literature ◽

Area Under The Curve ◽

Positive Likelihood Ratio ◽

Negative Likelihood Ratio ◽

High Morbidity ◽

Qualitative Synthesis

Abstract Glioblastoma (GBM) is the most malignant glioma cancer with a high morbidity and mortality worldwide. Unfortunately, a routine method is not available for screening or preoperative early detection of GBM. However, early detection in a none-invasive or minimally invasive method could be beneficial and increase the survival rate. In this systematic review and meta-analysis, we aimed to examine the diagnostic accuracy of exosomal RNAs that were extracted from patients’ CSF or serum for GBM diagnosis. We searched Web of Science, Scopus, PubMed (including Medline), Embase and ProQuest (as databases for grey literature) up to December 2019; we also performed backward and forward reference checking of included and relevant studies. Finally, included studies were assessed with QUADAS-2 checklist and their data extracted. We carried out a meta-analysis of included study, regarding to the diagnostic meta-analysis guidelines for obtaining pooled accuracy estimates. In addition, sensitivity analysis and meta-regression were also conducted. We retrived 1730 records from databases, nine of them included in systematic review and qualitative synthesis. Six studies were considered to statistical analysis and performed diagnostic meta-analysis. Our results suggested that the pooled sensitivity and specificity of exosomal biomarkers for GBM were 0.76 and 0.80, respectively. In addition, the pooled positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were 3.7, 0.30 and 12, respectively. The overall area under the curve (AUC) of exosomal biomarkers for GBM diagnosis was found to be 0.85. According to our results, the value of 0.85 for AUC, suggesting that exosomal biomarkers might serve as a high potential and non-invasive diagnostic tool for GBM.

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The value of miR-155 as a biomarker for the diagnosis and prognosis of lung cancer: a systematic review with meta-analysis

10.21203/rs.2.9996/v3 ◽

2019 ◽

Author(s):

Chuchu Shao ◽

Fengming Yang ◽

Zhiqiang Qin ◽

Xinming Jing ◽

Yongqian Shu ◽

...

Keyword(s):

Lung Cancer ◽

Systematic Review ◽

Likelihood Ratio ◽

Meta Analysis ◽

Positive Likelihood Ratio ◽

Disease Free Survival ◽

Negative Likelihood Ratio ◽

Free Survival ◽

Diagnosis And Prognosis ◽

Potential Biomarker

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Is neutrophil CD11b a special marker for the early diagnosis of sepsis in neonates? A systematic review and meta-analysis

BMJ Open ◽

10.1136/bmjopen-2018-025222 ◽

2019 ◽

Vol 9 (4) ◽

pp. e025222 ◽

Cited By ~ 1

Author(s):

Xia Qiu ◽

Jinhui Li ◽

Xiaoyan Yang ◽

Jun Tang ◽

Jing Shi ◽

...

Keyword(s):

Systematic Review ◽

Early Diagnosis ◽

Likelihood Ratio ◽

Neonatal Sepsis ◽

Meta Analysis ◽

Positive Likelihood Ratio ◽

Negative Likelihood Ratio ◽

Cochrane Library ◽

Post Test ◽

Sensitivity Specificity

ObjectivesOur study aimed to synthesise and analyse the early diagnostic value of neutrophil CD11b (nCD11b) for neonatal sepsis.DesignSystematic review and meta-analysis.MethodsPubmed, Embase, the Cochrane Library and Web of Science Databases were searched up to June 2018. We used Stata software (V.14.0) to conduct the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic OR (DOR), pretest probability, post-test probability and summary receiver operating characteristic (SROC) curve for diagnostic efficiency of n CD11b.ResultsNine studies, accounting for 843 neonates, were included. The overall pooled sensitivity, specificity, PLR, NLR, DOR, post-test positive probability and post-test negative probability and the area under the SROC curve were 0.82 (95% CI 0.71 to 0.90), 0.93 (95% CI 0.62 to 0.99), 11.51 (95% CI 1.55 to 85.62), 0.19 (95% CI 0.10 to 0.36), 59.50 (95% CI 4.65 to 761.58), 74%, 5% and 0.90, which had accuracy in diagnosing neonatal sepsis.ConclusionThe present evidence indicated that nCD11b is a promising biomarker for the early diagnosis of neonatal sepsis.

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Systematic Review and Meta-Analysis of the Diagnostic Accuracy of Mobile-Linked Point-of-Care Diagnostics in Sub-Saharan Africa

Diagnostics ◽

10.3390/diagnostics11061081 ◽

2021 ◽

Vol 11 (6) ◽

pp. 1081

Author(s):

Ernest Osei ◽

Sphamandla Josias Nkambule ◽

Portia Nelisiwe Vezi ◽

Tivani P. Mashamba-Thompson

Keyword(s):

Systematic Review ◽

Diagnostic Accuracy ◽

Likelihood Ratio ◽

Point Of Care ◽

Meta Analysis ◽

Positive Likelihood Ratio ◽

Negative Likelihood Ratio ◽

Sub Saharan Africa ◽

Point Of Care Diagnostics ◽

Sub Saharan

Mobile health devices are emerging applications that could help deliver point-of-care (POC) diagnosis, particularly in settings with limited laboratory infrastructure, such as Sub-Saharan Africa (SSA). The advent of Severe acute respiratory syndrome coronavirus 2 has resulted in an increased deployment and use of mHealth-linked POC diagnostics in SSA. We performed a systematic review and meta-analysis to evaluate the accuracy of mobile-linked point-of-care diagnostics in SSA. Our systematic review and meta-analysis were guided by the Preferred Reporting Items requirements for Systematic Reviews and Meta-Analysis. We exhaustively searched PubMed, Science Direct, Google Scholar, MEDLINE, and CINAHL with full text via EBSCOhost databases, from mHealth inception to March 2021. The statistical analyses were conducted using OpenMeta-Analyst software. All 11 included studies were considered for the meta-analysis. The included studies focused on malaria infections, Schistosoma haematobium, Schistosoma mansoni, soil-transmitted helminths, and Trichuris trichiura. The pooled summary of sensitivity and specificity estimates were moderate compared to those of the reference representing the gold standard. The overall pooled estimates of sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of mobile-linked POC diagnostic devices were as follows: 0.499 (95% CI: 0.458–0.541), 0.535 (95% CI: 0.401–0.663), 0.952 (95% CI: 0.60–1.324), 1.381 (95% CI: 0.391–4.879), and 0.944 (95% CI: 0.579–1.538), respectively. Evidence shows that the diagnostic accuracy of mobile-linked POC diagnostics in detecting infections in SSA is presently moderate. Future research is recommended to evaluate mHealth devices’ diagnostic potential using devices with excellent sensitivities and specificities for diagnosing diseases in this setting.

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Clinical value of thoracic ultrasonography in the diagnosis of pulmonary embolism: a systematic review and meta-analysis

Medical Ultrasonography ◽

10.11152/mu-3049 ◽

2021 ◽

Author(s):

Wu Chen ◽

Kun Xu ◽

Yiying Li ◽

Meifang Hao ◽

Yongsheng Yang ◽

...

Keyword(s):

Systematic Review ◽

Pulmonary Embolism ◽

Likelihood Ratio ◽

Meta Analysis ◽

Positive Likelihood Ratio ◽

Negative Likelihood Ratio ◽

Diagnostic Odds Ratio ◽

Cochrane Library ◽

Clinical Value ◽

Sensitivity Specificity

Aims: The present study investigated and evaluated the accuracy of thoracic ultrasonography (TUS) in the diagnosis of pulmonary embolism (PE) by conducting a systematic review and meta-analysis. Material and methods: The PubMed, Em-base and the Cochrane library databases were searched till March 2019 to retrieve relevant articles and the overall diagnostic accuracy of TUS in PE diagnosis was evaluated by meta-analysis. Results: Overall, 16 studies including 1,916 patients were enrolled in this meta-analysis. Of these, 762 (39.8%) had confirmed PE. The overall sensitivity, specificity, and area under the ROC curve (AUC) of TUS for PE were 82% (95% confidence interval (CI), 72%–88%), 89% (95% CI, 79%–95%), and 0.91 (95% CI, 0.88–0.93), respectively. Other efficacy parameters assessed demonstrated a positive likelihood ratio (PLR) of (7.6; 95% CI, 4.0–14.5), negative likelihood ratio of (NLR) (0.21; 95% CI, 0.14–0.30), and diagnostic odds’ ratio (DOR) of (36.86; 95% CI, 21.41–63.48). Conclusions: The current study suggested that although TUS cannot safely rule out PE, it is likely to be used as an aid or guidance to establish procedures and help to improve the diagnostic deficits in patients with PE.

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