Circulating miRNAs as novel potential biomarkers for esophageal squamous cell carcinoma diagnosis: a meta-analysis update

Abstract

Early detection of esophageal squamous cell carcinoma (ESCC) is urgently needed to reduce the high morbidity and mortality of disease. Circulating microRNAs (miRNAs) are promising molecular biomarkers for ESCC prediction. We performed a comprehensive meta-analysis to systematically evaluate the diagnostic accuracy of circulating miRNAs in diagnosis of ESCC patients. Eligible studies were identified and assessed for quality employing multiple search strategies. Summary estimates for sensitivity, specificity, and other measures of accuracy of miRNAs in the diagnosis of ESCC were pooled using the bivariate random effects model. A total of 27 studies from 11 published articles were included in the meta-analysis. The overall sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of circulating miRNAs for the diagnosis of ESCC were 79.9% (95% confidence intervals [CI]: 76.2%-83.1%), 81.3% (95% CI: 75.7-85.9), 4.27 (95%CI: 3.27-5.58), 0.25 (95% CI: 0.21-0.29), and 17.29 (95% CI: 12.01-24.86), respectively. The area under the summary receiver operating characteristic curve was 0.87 (95% CI: 0.84-0.90). The subgroup analyses based on research country (China vs. Japan), specimen type (plasma vs. serum), miRNAs profiling (single vs. multiple), and test method (screening vs. candidate; Taqman vs. SYBR) indicated no significant difference in the diagnostic accuracy of each subgroup. Collectively, our findings indicate that circulating miRNAs have significant potential to be used as noninvasive biomarkers for early detection of ESCC. Moreover, the subgroup analyses demonstrated the feasibility of using blood miRNAs as an ESCC diagnostic biomarker in Japanese and Chinese populations. Further, both plasma and serum are recommended as clinical specimens for miRNA detection. Further studies will be needed to validate these findings using larger numbers of patients.

Circulating plasma microRNAs in the detection of esophageal squamous cell carcinoma

“…Among them, miR-223 was the most significantly upregulated (fold change, 3.88) and miR-21 had the highest diagnostic value (AUC, 0.80). None of the miRNAs were associated with sex or age, which was in accordance with previous reports (21,58,59). All 5 miRNAs were associated with the T and N TNM stages, with the exception of miR-21, which was associated only with T stage.…”

“…MiRNAs continue to attract research attention for this purpose, and promising diagnostic markers have been identified for breast cancer (13), liver cancer (14), lung cancer (15), colorectal cancer (16), uterine cancer (17), glioma (18) and gastroesophageal cancer (19); a number of such biomarkers function as oncogenes or tumor-suppressor genes (20). Numerous studies have associated various circulating miRNAs with EC (21). However, different research groups have drawn contrasting conclusions regarding the same plasma miRNAs in EC.…”

Diagnostic and Prognostic Value of Circulating MicroRNAs for Esophageal Squamous Cell Carcinoma: a Systematic Review and Meta-analysis

“…This suggests that these microRNAs can be used as biomarkers for cancers. Thousands of microRNAs have been discovered, some of which have significant diagnostic and prognostic value in ESCC 16 . To comprehensively analyze the value of microRNAs as biomarkers, we performed a meta-analysis of each microRNA, while more literatures than previous meta-analyses were included.…”

“…However, one of the meta-analyses investigated the value of diagnosis and prognosis of single microRNA 12 . Moreover, several researchers combined various microRNAs to get conclusions about the value of all microRNAs in ESCC, but overlooked the heterogeneity in diverse microRNAs from inconsistent sample sources 13 - 16 . Taking into consideration the drawbacks of previous publications, a more integrative meta-analysis of microRNA for ESCC, on the basis of all relevant prior studies, was conducted to acquire a better understanding of the diagnostic and prognostic efficiency of microRNA in ESCC.…”

Identification of Novel Circulating miRNA Biomarkers for the Diagnosis of Esophageal Squamous Cell Carcinoma and Squamous Dysplasia

“…Furthermore, because of their high stability in circulation, blood miRNAs are ideal candidates as biomarkers for noninvasive diagnostic screening and for monitoring of cancer development (14). Although still an emerging area of research, our recent meta-analysis has highlighted the potential use of specific plasma/serum miRNAs in the detection of ESCC (15). However, most of these miRNAs were not further validated in independent case-control studies, and most studies only focused on a single miRNA rather than their combination.…”