Circulating microRNA/isomiRs as novel biomarkers of esophageal squamous cell carcinoma

Abstract

Background MicroRNA (miR)s are promising diagnostic biomarkers of cancer. Recent next generation sequencer (NGS) studies have found that isoforms of micro RNA (isomiR) circulate in the bloodstream similarly to mature micro RNA (miR). We hypothesized that combination of circulating miR and isomiRs detected by NGS are potentially powerful cancer biomarker. The present study aimed to investigate their application in esophageal cancer.

The Diagnostic and Prognostic Value of a Liquid Biopsy for Esophageal Cancer: A Systematic Review and Meta-Analysis

“…The first report that investigated the potential of miRNAs as diagnostic markers was published in 2008 [ 46 ]. There are abundant studies on circulating miRNAs in many cancers, including EC, and several researchers have combined several miRNAs to improve their diagnostic value [ 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 ]. Currently, molecular science technology has been constantly evolving, and microarray and NGS platforms have made it possible to perform comprehensive gene analysis using liquid biopsies [ 53 , 59 , 60 , 65 , 66 , 68 , 69 ].…”

“…Therefore, we evaluated the pooled AUC value using the random effect model, and the pooled AUC was 0.79 (0.75–0.83). These results confirmed that the copy number of ctDNA (AUC = 0.99, 95% CI = 0.98–1.00) [ 95 ], combination of metabolites (AUC = 0.96, 95% CI = 0.94–0.99) [ 80 ], and the combination of miRNAs (miR-30a-5p, 205-5p, and 574-3p) (AUC = 0.95, 95% CI = 0.90–1.00) [ 64 ] seemed to be a favorable candidate for the early detection of ECs.…”

“…Next, the derived sensitivity and 1-specificity values from each report (a total of thirty-two molecules from 22 studies [ 49 , 50 , 54 , 56 , 57 , 58 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 72 , 75 , 78 , 79 , 80 , 95 , 96 , 97 ]) were plotted ( Figure 4 c). The logarithmic regression curve, with 95% CIs, was constructed to evaluate the heterogeneity of each diagnostic value, and three molecules (lncSNHG1 [ 63 ], miR-216a [ 67 ], and a combination of miRNAs (miR16-5p, miR197-5p, and miR92a-3p) [ 58 ]) were considered as favorable candidates for the early detection of ECs.…”

“…The other was that most studies in this review used single molecules as diagnostic predictors. Another cancer meta-analysis, as described above, applied a combination of multiple molecules and the copy-number of ctDNA as a comprehensive marker (AUC = 0.99, 95% CI = 0.98–1.00), as well as a combination of miR-30a-5p, miR-205-5p, and miR-574-3p (AUC = 0.95, 95% CI = 0.90–1.00) [ 64 ], demonstrating a favorable diagnostic value. These results suggest that it might be difficult to determine a single definitive biomarker for cancer diagnosis and that exhaustive analysis will be required.…”

isomiRs–Hidden Soldiers in the miRNA Regulatory Army, and How to Find Them?

“…The accumulated evidence shows that the analysis of isomiRs expression pattern can differentiate tumor cells from normal, and moreover to discriminate amongst different tumor types and subtypes [ 118 , 119 ]. This strongly suggests isomiRs as potentially valuable diagnostic and prognostic biomarkers in cancer diagnostics [ 119 , 120 , 121 ]. Furthermore, the combination of isomiR features with state-of-the-art algorithms effectively differentiated normal from cancer cell lines [ 118 , 122 ].…”