Multiple miRNA Assays Research Articles

Diagnostic value of circulating microRNAs in thyroid carcinoma: A systematic review and meta‐analysis

Thyroid cancer (TC) is the most common endocrine system tumour. Several studies had revealed the potential of circulating microRNAs (miRNAs) as novel biomarkers for the diagnosis of TC. The purpose of this meta-analysis is to summarize published studies and evaluate the diagnostic accuracy of circulating miRNAs in TC detection. In this meta-analysis, we systematically searched three databases: PubMed, EMBASE and Cochrane Library. We used the bivariate mixed-effects regression model to calculate the pooled diagnostic parameters and conduct the summary receiver operator characteristic curve (SROC). All calculations were performed using stata software. Thirty-five studies from 9 articles, including 663 TC patients, 519 patients with benign thyroid nodules (BTNs), and 84 healthy controls were included in this meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and area under the SROC curve (AUC) were 0.81 (95% CI 0.75-0.86), 0.81 (95% CI 0.75-0.86), 4.3 (95% CI 3.2-5.6), 0.24 (95% CI 0.18-0.31), 18 (95% CI 12-28) and 0.88 (95% CI 0.85-0.90), respectively in BTN controls, and 0.81 (95% CI 0.75-0.86), 0.85 (95% CI 0.75-0.91), 5.3 (95% CI 3.3-8.7), 0.23 (95% CI 0.18-0.29), 24 (95% CI 14-39), 0.89 (95% CI 0.86-0.91) in healthy controls. The subgroup analysis found that multiple miRNA assays had higher diagnostic accuracy than single miRNA assays with sensitivity of 0.88, specificity of 0.89 and AUC of 0.94. Circulating miRNAs have good values to diagnose TC and distinguish TC patients from BTN patients. MiRNAs can assist in the diagnosis of malignancy and avoid unnecessary surgery. In summary, circulating miRNAs should be added to our current clinical tools.

The diagnostic value of circulating microRNAs as a biomarker for gastric cancer: A meta‑analysis.

Recently, cancer research microRNA studies have drawn great attention. However, the results of these studies have been inconsistent and variable regarding the availability of circulating miRNAs in gastric cancer (GC) diagnosis. Thus, results should be interpreted cautiously. The purpose of the present study was to assess the diagnostic performance of circulating miRNAs in GC diagnosis. We conducted a systematic and comprehensive approach for the inclusion of studies. The sensitivity, specificity, and diagnostic odds ratio were pooled with random effects models, and a summary of receiver operator characteristic (SROC) curves were plotted. The potential heterogeneity was assessed with Q test and I2 statistics. Subgroup analyses and meta-regressions further investigated the sources of heterogeneity. A total of 77 studies from 48 articles were eligible for the meta-analysis. The results revealed a sensitivity of 0.76, a specificity of 0.81, and an AUC of 0.86 for gastric cancer diagnosis with circulating miRNAs. In addition, subgroup analyses indicated that multiple miRNAs assays, non-microarray screening approaches, and serum-based miRNA assays exhibited good diagnostic performance in contrast to a single miRNA assay, microarray expression profiling screening, and plasma-based miRNA group analysis. The diagnostic ability of miRNAs in early stage I–II groups and the high expression group were approximately similar to that in the stage I–IV groups and the low expression group. For the circulating miRNAs, our meta-analysis identified a combination of multiple miRNAs, non-microarray chip screening, and serum-based miRNA assays were associated with the most effective GC diagnostic performance. However, many unclear molecular mechanisms limited the accuracy of the diagnostic results, and should be interpreted with caution. Further large-scale prospective studies are required for validating the diagnostic applicability of circulating miRNAs in gastric cancer patients.

Identification of circulating microRNAs as diagnostic biomarkers for ovarian cancer:A pooled analysis of individual studies.

Circulating microRNAs (miRNAs) are proposed as promising non-invasive diagnostic biomarkers for many cancers. However, the diagnostic value of circulating miRNAs in ovarian cancer is inconsistent in different studies. Thus we performed this meta-analysis to systematically evaluate the diagnostic value of circulating miRNAs in ovarian cancer. Eligible studies that were published prior to 30 June 2017 were searched from the PubMed, EMBASE, Cochrane Library, and Chinese National Knowledge Infrastructure. All analyses were performed using STATA 12.0 software. A bivariate regression was used to calculate pooled diagnostic accuracy estimates. A total of 36 studies from 16 publications were included in this meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of circulating miRNAs for ovarian cancer diagnosis were 0.76 (95% confidence intervals (CI): 0.69, 0.81), 0.81 (95% CI 0.74, 0.87), 4.00 (95% CI 2.70, 5.30), 0.30(95% CI 0.24, 0.37) and 13.00 (95% CI 9.00, 19.00), respectively. The area under the summary receiver operating characteristic curve was 0.85 (95% CI 0.82, 0.88). Subgroup analyses showed that multiple miRNA assays yielded better diagnostic characteristics than a single miRNA assay, and plasma miRNAs were better than serum miRNAs for ovarian cancer detection. Circulating miRNAs, especially the combination of multiple circulating miRNAs, are promising biomarkers for the diagnosis of ovarian cancer. However, further large-scale prospective studies are necessary to validate the applicability of the miRNAs in the early detection of ovarian cancer.

MicroRNAs as noninvasive biomarkers in bladder cancer detection: a diagnostic meta-analysis based on qRT-PCR data.

As the diagnostic significance of microRNAs (miRNAs) in the detection of bladder cancer is controversial, we aimed to perform a meta-analysis to comprehensively assess the diagnostic value of miRNAs in blood and urine for detecting bladder cancer. A systematic literature search of public databases was conducted to obtain qualified studies. Sensitivity was utilized to plot the summary receiver operator characteristic (SROC) curve against specificity and the area under the SROC curve (AUC) was generated to evaluate the pooled diagnostic efficiency. Subgroup analyses and meta-regression were applied to investigate the underlying sources of heterogeneity. The STATA 12.0 software was used to perform all statistic analyses. A total of 58 studies from 22 articles comprising 4,558 bladder cancer patients and 4,456 controls were included in our meta-analysis. MiRNAs in blood and urine manifested relatively good diagnostic efficiency in detecting bladder cancer, with a sensitivity of 0.74, a specificity of 0.78, and an AUC of 0.83. Multiple-miRNA assays were more accurate than single-miRNA ones in bladder cancer diagnosis. Blood-based miRNA assays displayed better diagnostic performance than urine-based ones. In addition, miRNAs showed reduced diagnostic value in bladder cancer among Caucasians compared with Asians. MiRNAs in blood and urine, especially the combination of multiple miRNAs, may serve as hopeful noninvasive biomarkers for early diagnosis of bladder cancer. Further extensive prospective research is needed to verify their clinical significance in bladder cancer diagnosis.

Urine microRNAs as biomarkers for bladder cancer: a diagnostic meta-analysis.

BackgroundThe diagnostic value of microRNA (miRNA) detection in patients with bladder cancer (BCa) is controversial. We performed a diagnostic meta-analysis to evaluate current evidence on the use of miRNA assays to diagnose BCa.MethodsWe systematically searched PubMed, Embase, and Web of Science for studies published before March 31, 2015. The pooled sensitivity, specificity, positive and negative likelihood ratios, diagnostic odds ratio, and area under the curve (AUC) were calculated to evaluate the overall test performance. Subgroup analyses were used to explore the between-study heterogeneity. Deeks’ funnel plot asymmetry test was used to test publication bias. We applied the software of RevMan 5.2 and Stata 11.0 to the meta-analysis.ResultsA total of 23 studies from nine articles were included in the meta-analysis, with a total of 719 patients and 494 controls. The pooled sensitivity and specificity were 0.75 (95% confidence interval [CI], 0.68–0.80) and 0.75 (95% CI, 0.70–0.80), respectively. The pooled positive likelihood ratio was 3.03 (95% CI, 2.50–3.67); negative likelihood ratio was 0.33 (95% CI, 0.27–0.42); and diagnostic odds ratio was 9.07 (95% CI, 6.35–12.95). The pooled AUC was 0.81 (95% CI, 0.78–0.85). Subgroup analyses indicated that the multiple miRNAs assays and urine supernatant assays showed high accuracies in diagnosing BCa.ConclusionThe miRNA assays may serve as potential noninvasive diagnostic tool for the detection of BCa. However, the clinical application of miRNA assays for BCa diagnosis still needs further validation by large prospective studies.

MicroRNAs as a potential tool in the differential diagnosis of thyroid cancer: a systematic review and meta-analysis.

Thyroid cancer is the most common endocrine malignancy, and its incidence has been increasing over the last 30 years. Several studies have suggested that miRNAs may play a significant role in the differential diagnosis of indeterminate thyroid nodules. To systematically evaluate the utility of miRNAs in discriminating malignant thyroid nodules from benign ones on fine-needle aspiration biopsy (FNAB) samples, a systematic review and meta-analysis of the published literatures were carried out. Three hundred and sixty-one samples, obtained from 341 patients, were included in the research, and summary sensitivities (SEN), specificities (SPE), positive likelihood ratios, negative likelihood ratios and diagnostic odds ratio were calculated. Then, summary receiver operating characteristic curves (SROCs) and areas under the SROC curves (AUCs) were calculated to further estimate the overall diagnostic value of miRNAs in thyroid cancer. The overall pooled SEN, SPE and AUC are 0·75, 0·81 and 0·89, respectively. For multiple miRNAs assays, the pooled SEN, SPE and AUC are 0·87, 0·75 and 0·68, respectively. For single miRNA assays, the corresponding results are 0·71, 0·84 and 0·87, respectively. The corresponding statistical results for differentiating indeterminate FNAB samples are 0·92, 0·68 and 0·86, respectively. Our current meta-analysis suggests that miRNAs may serve as a novel diagnostic tool in distinguishing malignant thyroid nodules from benign ones on FNAB specimens. In addition, subgroup analysis suggests that a panel of miRNAs may have a higher sensitivity but a relatively lower specificity than that of single miRNA in distinguishing thyroid nodules.

MicroRNAs as novel biomarkers for the differentiation of malignant versus benign thyroid lesions: a meta-analysis.

The aim of this meta-analysis was to systematically evaluate the diagnostic accuracy of microRNAs (miRNAs) in distinguishing malignant thyroid lesions from benign ones and to determine the potential of miRNAs as diagnostic biomarkers for thyroid cancer. The random-effect model was used to summarize the pooled estimates of diagnostic accuracy, including sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR). The summary receiver-operating characteristic curve (SROC) and area under the SROC curve (AUC) were used to further evaluate the overall diagnostic value. Overall, 20 studies from 7 articles, including 266 thyroid cancer patients and 277 controls with benign thyroid disease, were available for analysis. The pooled sensitivity, specificity, PLR, NLR, and DOR were: 0.78 (95%CI = 0.74-0.81), 0.73 (95%CI = 0.69-0.77), 3.17 (95%CI = 2.28-4.40), 0.30 (95%CI = 0.23-0.39), and 12.6 (95%CI = 8.26-19.4), respectively, and the AUC value was 0.85. The multiple miRNA assay yielded better diagnostic performance than the single miRNA assay, with sensitivity of 0.90 versus 0.75, specificity of 0.86 versus 0.71, PLR of 6.14 versus 2.71, NLR of 0.13 versus 0.36, DOR of 44.5 versus 8.81, and AUC of 0.95 versus 0.82, suggesting that the multiple miRNA assay is a more credible method for thyroid cancer detection. In summary, miRNA assays, especially multiple miRNA assays, may play an important role as a second-line diagnostic tool to improve the diagnostic accuracy of fine needle aspiration biopsy in indeterminate lesions. However, further studies are warranted to confirm our findings.

The expression and clinical significance of microRNAs in colorectal cancer detecting.

MicroRNAs (miRNAs) are small non-coding RNAs which regulate gene expressions post-transcriptionally. Nowadays, various miRNAs have been found to be sensitive and specific biomarkers for the early diagnosis of colorectal cancer (CRC); however, there are different, even conflicting results in different publications concerning the diagnostic accuracy of miRNA. Therefore, we aim to conduct a meta-analysis of the relevant publications to comprehensively evaluate the diagnostic value of miRNAs in CRC detection. Several public databases such as PubMed, Embase, and Google Scholar were retrieved up to July 13, 2014. Sensitivity was applied to plot the summary receiver operator characteristic (SROC) curve against specificity. The area under the SROC curve (AUC) was calculated to assess the classified effects. STATA 12.0 software was used to perform all statistic analyses. A total of 29 articles, including 80 studies, were involved in our meta-analysis, 55 of which focus on single-miRNA assays and the other 25 on multiple-miRNA assays. Our results suggested that multiple-miRNA assays show a better diagnostic accuracy compared with single-miRNA assays. In addition, blood-based miRNA assays were more accurate than feces-based miRNA assays in CRC diagnosis. Our results also showed that miRNA diagnosis appear to be more accurate in Asians than in Caucasians. However, further researches are needed to validate our results and the feasibility of miRNAs as biomarkers in routine clinical diagnosis of CRC.

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.

Diagnostic value of circulating microRNAs for gastric cancer in Asian populations: a meta-analysis.

Gastric cancer (GC) accounts for one of the highest mortality worldwide and particularly in East Asia. Many studies have reported on the potential value of microRNAs (miRNAs) detection for diagnosing GC, but their results have proven inconclusive. The present meta-analysis was conducted to assess the diagnostic value of circulating miRNAs for GC diagnosis. A literature search was carried out in databases (PubMed, Embase, Web of Science, The Cochrane Library, and CNKI) and other sources using combinations of keywords relating to GC, miRNAs, and diagnosis. The values of sensitivity, specificity, positive likelihood ratios (PLR), negative likelihood ratios (NLR), and diagnostic odds ratio (DOR) reported in individual studies were pooled using random-effects models. Potential sources of heterogeneity were assessed with subgroup and meta-regression analyses. The summary receiver operating characteristic (SROC) curve and the area under the curve (AUC) were used to assess the diagnosis accuracy of miRNAs. This meta-analysis included 1,279 patients with GC and 954 healthy controls from 20 publications. The pooled sensitivity, specificity, PLR, NLR, DOR, and AUC were 0.78 (95% CI: 0.73-0.81), 0.80 (95% CI: 0.76-0.84), 4.0 (95% CI: 3.1-6.0), 0.28 (95% CI: 0.23-0.34), 14 (95% CI: 10-21), and 0.86 (95% CI: 0.83-0.89), respectively. Subgroup analyses showed that early stages (I and II) GC were more easily detected than later stages and that multiple miRNAs assays were more accurate than single miRNA assays. Our meta-analysis suggests that miRNAs have a high diagnostic value for GC, especially in its early stages (I and II). In addition, multiple miRNAs assays have a better diagnosis value than single miRNA assays. In conclusion, circulating miRNAs might be used as noninvasive biomarkers for the confirmation of GC detection in Asian populations.

MicroRNAs as ideal biomarkers for the diagnosis of lung cancer.

Lung cancer (LC) is one of the most prevalent causes of cancer death with a high mortality rate worldwide. While various sets of microRNAs (miRNAs) have been found to be highly sensitive and specific biomarkers for the early diagnosis of LC (the first word of abstract), conflicting results on their diagnostic accuracy are still present in individual studies. Thus, we aimed to conduct a systematic review and meta-analysis of the published literature to comprehensively assess the diagnostic value of miRNAs for predicting LC. The sensitivity and specificity of each included study were used to plot the summary receiver operator characteristic (SROC) curve and to calculate the area under the SROC curve (AUC). All analyses were performed using the Stata 12.0 software. Twenty-six articles were involved in our meta-analysis, 18 of which focused on single miRNA assays and 15 on multiple miRNA assays. For single miRNA profiling, the pooled parameters calculated from all studies are as follows: sensitivity (SEN), 0.72; specificity (SPE), 0.74; positive likelihood ratio (PLR), 2.7; negative likelihood ratio (NLR), 0.39; and diagnostic odds ratio (DOR), 7. For multiple miRNA profiling, the pooled estimates for the overall studies are as follows: SEN, 0.81; SPE, 0.84; PLR, 4.9; NLR, 0.23; and DOR, 22, which are significantly better than the diagnostic performance of the single miRNA profiling. In addition, subgroup analyses based on sample types suggested that blood-based multiple miRNA assays were more accurate than non-blood-based studies. In conclusion, the current meta-analysis shows that multiple miRNA assays were more accurate in diagnosing LC than single miRNA assays. However, further large-scale investigations are urgently needed to confirm our results and verify the feasibility of routine clinical utilization.

Identification of circulating microRNAs as biomarkers in diagnosis of hematologic cancers: a meta-analysis.

Recent studies have provided new insights into the diagnostic value of circulating microRNAs (miRNAs) for hematologic cancers. However, inconsistent results have been reported on the diagnostic performance of various kinds of miRNAs. To systematically assess the potential diagnostic value of miRNAs in hematologic cancers, we conducted the present meta-analysis. Multiple databases (PubMed, Cochrane Library, EMBASE, CNKI, and Wan Fang) were carefully searched for available studies up to April 4, 2014. Sensitivity and specificity were pooled using a random-effects model. Likelihood ratio (LR), diagnostic odds ratio (DOR), and the area under the curve (AUC) were used to measure the diagnostic values. Subgroup and meta-regression analyses were used to find potential sources of heterogeneity. Thirty-four studies from 14 publications, which involved 1,159 hematologic cancer patients and 826 healthy controls, were included in this meta-analysis. The pooled estimates indicated a moderately high diagnostic accuracy for circulating miRNAs, with a sensitivity of 0.83, a specificity of 0.85, a PLR of 5.7, a NLR of 0.20, a DOR of 29, and an AUC of 0.91. The subgroup analyses showed that diagnostic accuracy was better for acute myeloid leukemia (AML) patients and Asians compared with other subgroups. In addition, multiple miRNA assays displayed a better performance than single ones. Furthermore, we found that plasma might be a more promising matrix for detecting the expression of miRNAs than serum. Our results identified the potential use of circulating miRNAs in second-line diagnosis for hematologic cancers, especially the value of miRNA panels. However, further large cohort studies are still required to confirm our findings.

Diagnostic value of microRNAs in discriminating malignant thyroid nodules from benign ones on fine-needle aspiration samples.

Many studies have suggested that microRNAs (miRNAs) might serve as novel diagnostic indicators of thyroid cancer (TC). However, inconsistent results have also been reported. This meta-analysis was conducted to assess the diagnostic value of miRNAs in discriminating malignant thyroid nodules from benign ones on fine-needle aspiration samples. A systematic literature search for relevant literature published up to April 5, 2014 was conducted in PubMed, Embase, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biological Medicine (CBM) databases. Data from different studies were pooled to estimate the summary sensitivity (SEN), specificity (SPE), positive likelihood ratios (PLR), negative likelihood ratios (NLR), diagnostic odds ratio (DOR), using the random-effect model. Summary receiver operator characteristic curves (SROCs) were plotted and areas under the SROC curve (AUC) were calculated to evaluate the overall test performance. Between-study heterogeneity was tested using the Q tests and the I (2) statistics. Potential sources of heterogeneity were analyzed through subgroup analyses and meta-regression. Deeks' funnel plot asymmetry test was performed to evaluate publication bias. All analyses were performed using STATA 12.0 software. Eighteen studies from 7 articles, including 543 patients with malignant thyroid nodules (n = 266) and benign ones (n = 277), were included in this meta-analysis. The pooled SEN was 0.77 (95 % CI: 0.70-0.83), SPN was 0.75 (95 % CI: 0.68-0.81), PLR was 3.1 (95 % CI: 2.4-4.0), NLR was 0.30 (95 % CI: 0.23-0.39), DOR was 10 (95 % CI: 7-16), and AUC was 0.83 (95 %CI: 0.79-0.86). Subgroup analyses indicated that multiple miRNAs assays showed a higher diagnostic accuracy than single miRNA assays. In conclusion, this meta-analysis suggests that miRNAs analysis can significantly improve diagnostic accuracy for differentiating malignant thyroid nodules from benign indeterminate ones on fine-needle aspiration (FNA) samples. With further confirmation, multiple miRNAs assays may play a critical role as a complement to fine-needle aspiration biopsy (FNAB).