Discovery and validation of methylation signatures in circulating cell-free DNA for early detection of esophageal cancer: a case-control study

Abstract

Background Plasma cell-free DNA (cfDNA) methylation has shown promising results in the early detection of multiple cancers recently. Here, we conducted a study to investigate the performance of cfDNA methylation in the early detection of esophageal cancer (ESCA). Methods Specific methylation markers for ESCA were identified and optimized based on esophageal tumor and paired adjacent tissues (n = 24). Age-matched participants with ESCA (n = 85), benign esophageal diseases (n = 10), and healthy controls (n = 125) were randomized into the training and test sets to develop a classifier to differentiate ESCA from healthy controls and benign esophageal disease. The classifier was further validated in an independent plasma cohort of ESCA patients (n = 83) and healthy controls (n = 98). Results In total, 921 differentially methylated regions (DMRs) between tumor and adjacent tissues were identified. The early detection classifier based on those DMRs was first developed and tested in plasma samples, discriminating ESCA patients from benign and healthy controls with a sensitivity of 76.2% (60.5–87.9%) and a specificity of 94.1% (85.7–98.4%) in the test set. The performance of the classifier was consistent irrespective of sex, age, and pathological diagnosis (P > 0.05). In the independent plasma validation cohort, similar performance was observed with a sensitivity of 74.7% (64.0–83.6%) and a specificity of 95.9% (89.9–98.9%). Sensitivity for stage 0–II was 58.8% (44.2–72.4%). Conclusion We demonstrated that the cfDNA methylation patterns could distinguish ESCAs from healthy individuals and benign esophageal diseases with promising sensitivity and specificity. Further prospective evaluation of the classifier in the early detection of ESCAs in high-risk individuals is warranted.

DNA methylation markers in esophageal cancer

“…They tested the model in three independent cohorts and achieved good sensitivities (74.7%–86.0%) and specificities (94.0%–95.9%) ( Qiao et al, 2021 ). However, the sensitivity of this diagnostic model for stage 0-II esophageal cancer was only 58.8% ( Qiao et al, 2021 ).…”

An update of clinical value of circulating tumor DNA in esophageal cancer: a systematic review and meta-analysis

“…More recently, some studies have demonstrated the clinical value of circulating tumor DNA (ctDNA) for EC [ 11 , 12 ]. The ctDNA is defined as cell free DNA (cfDNA) released by necrotic and apoptotic cancer cells into the blood; and its diagnostic, therapeutic, and prognostic value have been widely studied.…”

Glutamine Deprivation Synergizes the Anticancer Effects of Cold Atmospheric Plasma on Esophageal Cancer Cells

“…Esophageal cancer is among the leading causes of cancer-related deaths worldwide [ 1 , 2 , 3 ]. The current mainstream treatments for esophageal cancer include esophagectomy, chemotherapy, radiotherapy, targeted therapy, multimodal therapy and recently, immunotherapy [ 4 ].…”