Saliva and blood miRNAs as complementary biomarkers for esophageal cancer detection

Mary Kathryn MaxwellTaichiro Nonaka^*

• Louisiana State University Health Shreveport, Shreveport, United States

Objective: Esophageal cancer is a highly aggressive malignancy with poor survival rates due to late-stage diagnosis. Early detection is crucial for improving prognosis, yet current diagnostic methods, such as endoscopy, are invasive and impractical for routine screening. Circulating microRNAs (miRNAs) have emerged as promising non-invasive biomarkers for cancer detection through liquid biopsy approaches. This meta-analysis aims to evaluate the diagnostic performance of circulating miRNAs in blood and saliva for esophageal cancer detection. Methods: A systematic literature search was conducted in PubMed, Web of Science, and Scopus to identify relevant studies published between 2004 and 2024. Eligible studies included those that evaluated miRNA expression in plasma, serum, or saliva of esophageal patients. The analysis assessed the diagnostic accuracy of circulating miRNAs in three distinct categories: combined blood-and saliva-derived miRNAs, blood-derived miRNAs, and saliva-derived miRNAs. Pooled sensitivity, specificity, summary receiver operating characteristic (SROC) curves, diagnostic likelihood ratios, and diagnostic odds ratios were evaluated to determine the reliability of these biomarkers. Results: A total of 27 articles encompassing 47 sub-studies with 2,396 patients were included in this meta-analysis. The pooled sensitivity of combined blood-and saliva-derived miRNAs for esophageal cancer diagnosis was 0.79 (95% CI: 0.76–0.82), with a specificity of 0.77 (95% CI: 0.72–0.80). Blood-derived miRNAs alone demonstrated a sensitivity of 0.77 and specificity of 0.79, while saliva-derived miRNAs alone exhibited higher sensitivity of 0.88 but lower specificity of 0.60. The area under the SROC curve (AUC) was 0.85 for both combined and blood-derived miRNAs, and 0.83 for saliva-derived miRNAs, demonstrating strong overall diagnostic accuracy. Diagnostic odds ratios further supported the clinical utility of miRNA biomarkers. Deeks' funnel plot asymmetry test revealed no significant publication bias. Conclusion: Circulating miRNAs show strong potential as liquid biopsy biomarkers for the non-invasive diagnosis of esophageal cancer. While saliva-derived miRNAs exhibit higher sensitivity, blood-derived miRNAs provide greater specificity. These findings indicate the need for further validation and standardization of miRNA-based assays to facilitate their integration into clinical practice for early detection of esophageal cancer.