The authors revealed that the carcinogenic effect of piR-823 may result from its induced abnormal DNA methylation via DNMT3B. Additionally, an increased risk of lymph node metastasis is associated with a higher piR-823 level, and piR-823 exhibits high specificity for detecting ESCC (AUC = 0.713), which suggests its potential as a diagnostic and prognostic biomarker. The gene discussed is DNMT3B; the disease is esophageal squamous cell carcinoma.