Objective: Delayed diagnosis of esophageal cancer (EC) contributes to its high mortality rate. The identification of reliable diagnostic biomarkers is therefore of critical importance. MicroRNAs (miRNAs) have emerged as promising biomarkers detectable in both tumor tissue and circulation. In the present study, we evaluated the expression pattern of miR-338-3p in a population of Iranian patients with esophageal squamous cell carcinoma (ESCC). Materials and Methods: In this case-control study, formalin-fixed paraffin-embedded (FFPE) blocks of tumor specimens from 37 patients with ESCC, diagnosed between 2012 to 2013, were obtained from the pathology department at Mashhad University of Medical Sciences and used for routine histopathological evaluation and miRNA analysis. Patients included both sexes, with average age of 60.18 years old, and tumors classified to grade I–III. Paired adjacent non-tumor tissues served as controls. miR-338-3p expression was quantified in FFPE tissues using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). For functional analysis, miR-338-3p was overexpressed in KYSE-30 cells, and cell cycle distribution and apoptosis were analyzed using flow cytometry. Results: Analysis revealed a significant downregulation of microRNA-338-3p (miR-338-3p) in 37 participants with ESCC compared with adjacent non-tumor tissues (P<0.001). Receiver operating characteristic (ROC) curve analysis demonstrated that miR-338-3p expression could discriminate tumor from non-tumor samples with an area under the curve (AUC) of 0.8 (P<0.001), indicating acceptable diagnostic sensitivity and specificity. Functional assay in human KYSE-30 ESCC cells showed that overexpression of miR-338-3p resulted in more than a two-fold increase in the apoptotic cell population, as measured at sub-G1 peak by flow cytometry. Conclusion: Our findings indicate that miR-338-3p is downregulated in ESCC and exhibits potential as a diagnostic biomarker in this population of Iranian patients. Further studies are warranted to validate its clinical utility and potential role in targeted therapeutic strategies.

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