scholarly journals Diagnostic Role of Extracellular Vesicles in Cancer: A Comprehensive Systematic Review and Meta-Analysis

Author(s):  
Shu-ya Liu ◽  
Yin Liao ◽  
Hossein Hosseinifard ◽  
Saber Imani ◽  
Qing-lian Wen

Background: Cancer-derived extracellular vesicles (EVs) are regarded to have significant function in most steps during cancer progression. This meta-analysis aims to investigate the accuracy of EVs as a biomarker in cancer diagnosis.Methods: The diagnostic efficacy of EVs for different cancers was assessed using pooled sensitivity and specificity, diagnostic odds ratio (DOR), and overall area under the curve (AUC) of the summary receiver operating characteristic (SROC). The positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were verified to estimate the diagnostic efficacy of EV at a clinical level.Results: In all, 6,183 cancer patients and 2,437 healthy controls from 75 eligible studies reported in 42 publications were included in the study. The overall pooled sensitivity, specificity, PLR, NLR, and DOR were 0.62 (95% CI: 0.60–0.63), 0.76 (95% CI: 0.75–0.78), 3.07 (95% CI: 2.52–3.75), 0.34 (95% CI: 0.28–0.41), and 10.98 (95% CI: 7.53–16.00), respectively. Similarly, the AUC of the SROC was 0.88, indicating a high conservation of EVs as an early diagnostic marker. Furthermore, subgroup analysis suggested that the use of small EVs as a biomarker was more accurate in serum-based samples of nervous system cancer (p < 0.001). As a result, ultracentrifugation and quantification and size determination methods, such as Western blotting and ELISA were the most reliable identification methods for EV detection. We also indicated that increased secretion of EVs made them a capable biomarker for diagnosing cancer in elderly European individuals.Conclusions: Our study provides evidence that EVs are a promising non-invasive biomarker for cancer diagnosis. Well-designed cohort studies should be conducted to warrant the clinical diagnostic value of EVs.

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Tian-Ao Xie ◽  
Ye-Ling Liu ◽  
Rui-Chun Meng ◽  
Xiao-Shan Liu ◽  
Ke-Ying Fang ◽  
...  

Background. Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are widely spread across the world. Asymptomatic or inconspicuous CT/NG infections are difficult to diagnose and treat. Traditional methods have the disadvantages of low detection rate, inaccurate results, and long detection time. However, Xpert CT/NG makes up for the aforementioned shortcomings and has research value and popularization significance. Methods. PubMed, Embase, Cochrane Library, and Web of Science were systematically searched, and studies were screened using Xpert CT/NG for diagnosing CT/NG. QUADAS-2 was used to evaluate the quality of the eligible studies. Then, two groups of researchers independently extracted data from these studies. Meta-analyses of sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and the area under the curve (AUC) of the summary receiver operating characteristic (SROC) curve were conducted using Meta-DiSc 1.4. Finally, Deek’s funnel plots were made using Stata 12.0 to evaluate publication bias. Results. 14 studies were identified, and 46 fourfold tables were extracted in this meta-analysis. The pooled SEN, SPE, PLR, NLR, DOR, and AUC in diagnosing CT were 0.94 (95% confidence interval (CI): 0.93–0.95), 0.99 (95% CI: 0.99–1.00), 97.17 (95% CI: 56.76–166.32), 0.07 (95% CI: 0.04–0.12), 1857.25 (95% CI: 943.78–3654.86), and 0.9960, respectively. The pooled SEN, SPE, PLR, NLR, DOR, and AUC in diagnosing NG were 0.95 (95% CI: 0.93–0.96), 1.00 (95% CI: 1.00–1.00), 278.15 (95% CI: 152.41–507.63), 0.08 (95% CI: 0.06–0.12), 4290.70 (95% CI: 2161.78–8516.16), and 0.9980, respectively. Conclusions. Xpert CT/NG had high diagnostic sensitivity and specificity for CT and NG. However, more evidence is required to confirm that Xpert CT/NG might serve as the primary method for detecting CT and NG and even the gold standard for diagnosis in the future.


2020 ◽  
Vol 7 ◽  
Author(s):  
Ying Luo ◽  
Ying Xue ◽  
Liyan Mao ◽  
Qun Lin ◽  
Guoxing Tang ◽  
...  

Background: Tuberculous peritonitis (TP) is a common form of abdominal tuberculosis (TB). Diagnosing TP remains challenging in clinical practice. The aim of the present meta-analysis was to evaluate the diagnostic accuracy of peripheral blood (PB) T-SPOT and peritoneal fluid (PF) T-SPOT for diagnosing TP.Methods: PubMed, EmBase, Cochrane, Scopus, Google scholar, China national knowledge internet, and Wan-Fang databases were searched for relevant articles from August 1, 2005 to July 5, 2020. Statistical analysis was performed using Stata, Revman, and Meta-Disc software. Diagnostic parameters including pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were determined. Summary receiver operating characteristic curve was used to determine the area under the curve (AUC).Results: Twelve studies were eligible and included in the meta-analysis. The analysis showed that the pooled sensitivity and specificity of PB T-SPOT in diagnosing TP were 0.91 (95% CI, 0.88–0.94) and 0.78 (95% CI, 0.73–0.81), respectively, while the pooled PLR, NLR, and DOR were 4.05 (95% CI, 2.73–6.01), 0.13 (95% CI, 0.07–0.23), and 37.8 (95% CI, 15.04–94.98), respectively. On the other hand, the summary estimates of sensitivity, specificity, PLR, NLR, and DOR of PF T-SPOT for TP diagnosis were 0.90 (95% CI, 0.85–0.94), 0.78 (95% CI, 0.72–0.83), 6.35 (95% CI, 2.67–15.07), 0.14 (95% CI, 0.09–0.21), and 58.22 (95% CI, 28.76–117.83), respectively. Furthermore, the AUC of PB T-SPOT and PF T-SPOT for TP diagnosis were 0.91 and 0.94, respectively.Conclusions: Our results indicate that both PB T-SPOT and PF T-SPOT can be served as sensitive approaches for the diagnosis of TP. However, the unsatisfactory specificities of these two methods limit their application as rule-in tests for TP diagnosis. Furthermore, the standardization of the operating procedure of PF T-SPOT is further needed.


2020 ◽  
Author(s):  
Ke Wang ◽  
Shan Cong ◽  
Tiangang Ma ◽  
Xin Di ◽  
Chang Tian ◽  
...  

Abstract The aim of the study was to conduct a meta-analysis to evaluate the accuracy of neutrophil CD64, procalcitonin (PCT), and interleukin-6 (IL-6) for the diagnosis of sepsis. The sample articles were searched in various databases to collect published studies on the diagnosis of sepsis by neutrophil CD64, PCT, and IL-6. By using the Stata SE 15.0 software, forest plots and the area under the summary receiver operating characteristic curves were drawn. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and area under the curve (AUC) were calculated. 54 articles were included in the study. The number of studies that evaluated the diagnostic value of neutrophil CD64, PCT, and interleukin-6 were 20, 39, and 15, respectively. The pooled sensitivity, specificity, and AUC of neutrophil CD64 for the diagnosis of sepsis were 0.88 [95% confidence interval (CI), 0.81–0.92], 0.88 (95% CI, 0.83–0.91), and 0.94 (95% CI, 0.91–0.96), respectively. The pooled sensitivity, specificity, and AUC of PCT for the diagnosis of sepsis were 0.82 (95% CI, 0.78–0.85), 0.78 (95% CI, 0.74–0.82), and 0.87 (95% CI, 0.83–0.89), respectively. Subgroup analysis showed that the AUC for PCT diagnosis of intensive care unit (ICU) sepsis was 0.86 (95% CI, 0.83–0.89) and the AUC for PCT diagnosis of non-ICU sepsis was 0.82 (95% CI, 0.78–0.85). The pooled sensitivity, specificity, and AUC of IL-6 for the diagnosis of sepsis were 0.72 (95% CI, 0.65–0.78), 0.70 (95% CI, 0.62–0.76), and 0.77 (95% CI, 0.73–0.80), respectively. Of the three biomarkers studied, neutrophil CD64 showed the highest diagnostic value for sepsis, followed by PCT, and IL-6. On the other hand, PCT showed a better diagnostic value for the diagnosis of sepsis in patients with severe conditions compared with that in patients with non-severe conditions.


2018 ◽  
Vol 3 (5) ◽  
pp. 273-279 ◽  
Author(s):  
Cheng Li ◽  
Nora Renz ◽  
Cristina Ojeda Thies ◽  
Andrej Trampuz

Abstract. Introduction: Periprosthetic joint infection (PJI) is the most serious complication after arthroplasty, and the diagnosis of PJI is still challenging with modern medical technology. To improve the diagnostic rate, combined diagnostic methods are gradually beginning to be used to diagnose PJI. Sonication is one accurate way to diagnose PJI, but there is minimal research regarding the diagnostic value of sonicate fluid (SF) in blood culture bottles (BCB). Therefore, we evaluated this combined diagnostic method by meta-analysis.Methods: We searched English publications in electronic databases regarding the use of sonicate fluid in blood culture bottles (SF-BCB) for diagnosing PJI, screened the literature according to inclusion criteria, assessed the quality of the selected literature, and collected information regarding SF-BCB.Results: This meta-analysis includes 4 studies that evaluated SF-BCB for the diagnosis of PJI. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) are 0.85 (95% Confidence interval [CI], 0.77 to 0.91), 0.86 (CI, 0.81 to 0.91), 5.34 (CI, 3.13 to 9.11), 0.16 (CI, 0.06 to 0.48) and 39.01 (CI, 9.04 to 168.35), respectively. The area under the curve (AUC) of the summary receiver operating characteristic (SROC) is 0.9186 (standard error, 0.0205).Conclusion: SF-BCB has great value for the microbiological diagnosis of PJ, especially for patients with prior antibiotic treatment.


2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Amir Hossein Aalami ◽  
Hossein Abdeahad ◽  
Mohammad Mesgari ◽  
Thozhukat Sathyapalan ◽  
Amirhossein Sahebkar

Aims. Bladder cancer (BCa) is a common cancer in North America and Europe that carries considerable morbidity and mortality. A reliable biomarker for early detection of the bladder is crucial for improving the prognosis of BCA. In this meta-analysis, we examine the diagnostic role of the angiogenin (ANG) protein in patients’ urine with bladder neoplasm. Methods. We performed a systematic literature search using ScienceDirect, Web of Science, PubMed/MEDLINE, Scopus, Google Scholar, and Embase, up to 10th October 2020 databases. Meta-Disc V.1.4 and Comprehensive Meta-Analysis V.2.2 software calculated the pooled specificity, sensitivity, area under the curve (AUC), diagnostic odds ratio (DOR), positive likelihood ratio (LR+), negative likelihood ratio (LR-), Q ∗ index, and summary receiver-operating characteristic (SROC) for the role of ANG as a urinary biomarker for BCa patients. Results. Four case-control studies were included with 656 participants (417 cases and 239 controls) in this meta-analysis. The pooled sensitivity of 0.71 (95% CI: 0.66–0.75), specificity of 0.78 (95% CI: 0.73–0.81), LR+ of 3.34 (95% CI: 2.02–5.53), LR- of 0.37 (95% CI: 0.32–0.44), DOR of 9.99 (95% CI: 4.69–21.28), and AUC of 0.789 and Q ∗ index of 0.726 demonstrate acceptable diagnostic precision of ANG in identifying BCa. Conclusion. This meta-analysis showed that ANG could be a fair biomarker for the diagnosis of BCa patients.


2015 ◽  
Vol 81 (6) ◽  
pp. 626-629 ◽  
Author(s):  
Bing Xiong ◽  
Baishu Zhong ◽  
Zhenwei Li ◽  
Feng Zhou ◽  
Ruying Hu ◽  
...  

The aim of the study is to evaluate the diagnostic accuracy of noncontrast CT in detecting acute appendicitis. Prospective studies in which noncontrast CT was performed to evaluate acute appendicitis were found on PubMed, EMBASE, and Cochrane Library. Pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were assessed. The summary receiver-operating characteristic curve was conducted and the area under the curve was calculated. Seven original studies investigating a total of 845 patients were included in this meta-analysis. The pooled sensitivity and specificity were 0.90 (95% CI: 0.86–0.92) and 0.94 (95% CI: 0.92–0.97), respectively. The pooled positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio was 12.90 (95% CI: 4.80–34.67), 0.09 (95% CI: 0.04–0.20), and 162.76 (95% CI: 31.05–853.26), respectively. The summary receiver-operating characteristic curve was symmetrical and the area under the curve was 0.97 (95% CI: 0.95–0.99). In conclusion, noncontrast CT has high diagnostic accuracy in detecting acute appendicitis, which is adequate for clinical decision making.


PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3136 ◽  
Author(s):  
Qianqian Liu ◽  
Wenzhang Li ◽  
Yunfeng Chen ◽  
Xinmiao Du ◽  
Chengdi Wang ◽  
...  

BackgroundThe diagnostic values of interferon-gamma release assays (IGRA) in tuberculosis (TB) vary a lot with different site of infections, with especially higher sensitivities in chronic forms of TB such as tuberculosis of the lymph node. We conducted a meta-analysis to comprehensively evaluate the overall accuracy of diagnostic IGRA for tuberculous lymphadenitis.MethodsPubmed, Web of Science, EMBASE, Wanfang and CNKI databases up to February 17, 2017 were searched to identify published studies. The study quality was evaluated using the QUADAS-2 checklist. The pooled estimates of diagnostic parameters were generated using a bivariate random-effects model and summary receiver operating characteristic (SROC) curves were used to summarize global performance.ResultsA total of ten qualified studies, performed in Korea or China, including 1,084 patients, were enrolled in this meta-analysis. The pooled estimates of diagnostic accuracy were as follows: sensitivity, 0.89 (95% CI [0.85–0.92]); specificity, 0.81 (95% CI [0.77–0.83]); positive likelihood ratio (PLR), 4.25 (95% CI [2.79–6.47]); negative likelihood ratio (NLR), 0.16 (95% CI [0.12–0.22]); and area under the curve (AUC) was 0.93. According to subgroup analyses, studies conducted using QuantiFERON-TB, in Korean population and focusing on cervical lymphadenitis exhibited relative higher specificity while lower sensitivity. No evidence of publication bias was identified.ConclusionsIGRA exhibits high diagnostic accuracy in tuberculous lymphadenitis. The diagnostic value of IGRA differed by different IGRA methods, ethnicity and lymphadenitis location. Our conclusion may be more applicable to population from TB prevalent areas.


2021 ◽  
Vol 20 ◽  
pp. 153303382110119
Author(s):  
Wen-Ting Zhang ◽  
Guo-Xun Zhang ◽  
Shuai-Shuai Gao

Background: Leukemia is a common malignant disease in the human blood system. Many researchers have proposed circulating microRNAs as biomarkers for the diagnosis of leukemia. We conducted a meta-analysis to evaluate the diagnostic accuracy of circulating miRNAs in the diagnosis of leukemia. Methods: A comprehensive literature search (updated to October 13, 2020) in PubMed, EMBASE, Web of Science, Cochrane Library, Wanfang database and China National Knowledge Infrastructure (CNKI) was performed to identify eligible studies. The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) for diagnosing leukemia were pooled for both overall and subgroup analysis. The meta-regression and subgroup analysis were performed to explore heterogeneity and Deeks’ funnel plot was used to assess publication bias. Results: 49 studies from 22 publications with a total of 3,489 leukemia patients and 2,756 healthy controls were included in this meta-analysis. The overall sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and area under the curve were 0.83, 0.92, 10.8, 0.18, 59 and 0.94, respectively. Subgroup analysis shows that the microRNA clusters of plasma type could carry out a better diagnostic accuracy of leukemia patients. In addition, publication bias was not found. Conclusions: Circulating microRNAs can be used as a promising noninvasive biomarker in the early diagnosis of leukemia.


2020 ◽  
Vol 2020 ◽  
pp. 1-14 ◽  
Author(s):  
Yao Jiang ◽  
Zuohong Hu ◽  
Zhihua Zuo ◽  
Yiqin Li ◽  
Fei Pu ◽  
...  

Background. Cervical cancer (CC) is one of the most common female malignant tumors. And cervical intraepithelial neoplasia (CIN) is the precancerous lesion of CC, which can progress to invasive CC. MicroRNAs (miRNAs) have been found to be potential diagnostic biomarkers for CIN or CC. However, recently, the lack of sufficient studies about the diagnostic value of miRNAs for CIN made it challenging to separately investigate the diagnostic efficacy of miRNAs for CIN. Likewise, the conclusions among those studies were discordant. Therefore, we conducted this meta-analysis, aimed at evaluating the diagnostic efficacy of miRNAs for CIN and CC patients. Methods. Literature search was performed in PubMed, Embase, and Web of Science databases. Pooled sensitivity, specificity, and other diagnostic parameters were calculated through Stata 14.0 software. Furthermore, subgroup analyses and metaregression analysis were conducted to explore the main sources of heterogeneity. Results. Ten articles covering 50 studies were eligible, which included 5,908 patients and 4,819 healthy individuals. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were 0.81 (95% CI, 0.77-0.85), 0.86 (95% CI, 0.83-0.89), 5.9 (95% CI, 4.5-7.7), 0.22 (95% CI, 0.17-0.28), 27 (95% CI, 17-44), and 0.91 (95% CI, 0.88-0.93), respectively. Additionally, the ethnicity and internal reference were the main sources of heterogeneity. Conclusions. Circulating miRNAs can be a promising noninvasive diagnostic biomarker for CIN and early CC, especially miR-9 and miR-205, which need to be verified by large-scale studies.


2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Daye Cheng ◽  
Ying Sun ◽  
Hu He

The diagnostic value of serum HE4 in patients with lung cancer remains controversial. Thus, we performed a systematic review and meta-analysis to assess the diagnostic accuracy of serum HE4 for lung cancer. We conducted a comprehensive literature search in PubMed, EMBASE, Chinese National Knowledge Infrastructure (CNKI), and WANFANG databases between Jan. 1966 and Nov. 2014. The diagnostic sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and summary receiver operating characteristic curve (SROC) were pooled by Meta-DiSc 1.4 software. A total of seven articles including 715 cases and 549 controls were included for analysis. The summary estimates for serum HE4 in the diagnosis of lung cancer in these studies were pooled SEN 0.72 (95% CI: 0.68–0.75), SPE 0.85 (95% CI: 0.81–0.88), PLR 4.68 (95% CI: 3.23–6.78), NLR 0.31 (95% CI: 0.24–0.39), and DOR 17.14 (95% CI: 9.72–30.20), and the area under the curve (AUC) was 0.8557. This meta-analysis indicated that serum HE4 is a potential tool in the diagnosis of lung cancer. In addition, considering the high heterogeneity and potential publication bias, further studies with rigorous design and large sample size are needed in the future.


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