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

Abstract

Background: Circulating miRNAs have been identified as diagnostic biomarkers for esophageal squamous cell carcinoma (ESCC), but their efficacy in discovering early-stage ESCC is still unsatisfying. Esophageal squamous dysplasia (ESD) is the precursor lesion of ESCC. Notably, little is known about the role(s) of circulating miRNAs in identifying ESD. In this study, we, therefore, aimed to identify serum miRNAs as novel diagnostic markers for detecting ESD and ESCC. Methods: The genome-wide miRNA expression was profiled in 104 (52 ESCC and 52 controls) serum samples using microarray. Seven candidate miRNAs from the microarray assay were evaluated for their diagnostic performance in another cohort of 266 participants (96 ESCC, 92 ESD, and 78 healthy controls). Results: The serum levels of miR-16-5p, miR-197-5p, miR-451a, and miR-92a-3p were associated with ESCC; the biomarker based on the panel of these four miRNAs could efficiently distinguish patients with ESCC from the controls [AUC ¼ 0.856; 95% confidence interval (CI), 0.794-0.905; P < 0.001]. The serum levels of miR-16-5p, miR-320c, miR-638, and miR-92a-3p were significantly higher in patients with ESD than in controls, and this four-miRNA signature could efficiently differentiate patients with ESD from the controls (AUC ¼ 0.842; 95% CI, 0.778-0.893; P < 0.001). In addition, compared with serum carcinoembryonic antigen and carbohydrate antigen 199, miRNA-based panels had a better diagnostic performance in distinguishing patients with ESCC and ESD from healthy controls. Conclusions: Our study identified two novel panels of circulating miRNAs with high efficiency in detecting ESCC and ESD, suggesting that circulating miRNAs, in particular the combination of them, might serve as noninvasive biomarkers for the early detection of ESCC. Impact: This study suggests the feasibility of using circular miRNA-based blood tests to aid in the detection of ESD and ESCC.

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 ].…”

“…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.…”

Circulating MiR-1290 as a Potential Diagnostic and Disease Monitoring Biomarker of Human Gastrointestinal Tumors

“…Research has demonstrated that miR-16-5p is up-regulated in numerous diseases, such as rheumatoid arthritis [17], breast cancer [18], and esophageal cancer [19], and serves as a potential disease marker. In our study, we also con rmed that miR-16-5p is overexpressed in the serum of breast cancer and rheumatoid arthritis patients, the expression levels of circulating miR-16-5p uctuate with changes of disease activity in gastrointestinal patients, and normalization with miR-16-5p might decrease variability, as discovered in previous research [7].…”

Artificial intelligence technique in detection of early esophageal cancer

“…It may be that the selection of characteristic secretory proteins in this study was based on genes up-regulated in tumor tissues and that the down-regulated genes were not fully utilized. In addition, Shen et al[ 48 ] and Zhai et al[ 49 ] used microRNA and protein markers specifically expressed in the plasma of ESCC patients to build diagnostic models and found that both of them could effectively distinguish esophageal squamous dysplasia (ESD) from healthy controls. However, compared with ESD or early ESCC, the AI-assisted gene diagnosis of BE-related dysplasia and early EAC is less studied.…”