Background: Esophageal cancer (EC) is a prevalent malignancy characterized by a low 5-year survival rate, primarily attributed to delayed diagnosis and limited therapeutic options. Currently, early detection of EC heavily relies on endoscopy and pathological examination, which pose challenges due to their invasiveness and high costs, leading to low patient compliance. The detection of DNA methylation offers a non-endoscopic, cost-effective, and secure approach that holds promising prospects for early EC detection.Methods: To identify improved methylation markers for early EC detection, we conducted a comprehensive review of relevant literature, summarized the performance of DNA methylation markers based on different input samples and analytical methods in EC early detection and screening.Findings: This review reveals that blood cell free DNA methylation-based method is an effective non-invasive method for early detection of EC, although there is still a need to improve its sensitivity and specificity. Another highly sensitive and specific non-endoscopic approach for early detection of EC is the esophageal exfoliated cells based-DNA methylation analysis. However, while there are substantial studies in esophageal adenocarcinoma, further more validation is required in esophageal squamous cell carcinoma.Conclusion: In conclusion, DNA methylation detection holds significant potential as an early detection and screening technology for EC.

Target gastrointestinal cancers (GICs), encompassing esophageal cancer (EC), gastric cancer (GC), and colorectal cancer (CRC), originate within a single readily accessible luminal organ system and are diagnosable using endoscopy. However, endoscopy is an invasive procedure with low compliance and no plasma-based DNA methylation assay for the early detection of GICs. Nine potential DNA methylation markers were identified and evaluated in tissue (n=60) and plasma (n=155) cohorts to select the most suitable markers. A training cohort (n=244) and a validation cohort (n=199), including GICs patients, benign tumors, gastrointestinal polyps, and controls, were enrolled to develop and validate a DNA methylation panel. An independent prospective cohort (n=158) was used to validate the panel's performance and compare it with blood protein tumor markers. Six out of nine candidate methylation markers with excellent discrimination abilities in both tissue and plasma cohorts were selected for the DNA methylation panel. The panel demonstrated high AUC values of 0.937 (EC), 0.968 (GC), and 0.987 (CRC) in training cohort, and achieved AUC values of 0.921 (EC), 0.921 (GC), and 0.959 (CRC) in validation cohort. Notably, it achieved impressive AUC values of 0.971 and 0.843 for identifying stage I GICs in the training and validation cohorts, respectively. In the prospective cohort, the six-marker panel showed comparable AUC values to CEA, AFP, and CA19-9 (0.935, 0.769, 0.663, and 0.668, respectively). This study successfully developed and validated a novel, robust, sensitive, and specific plasma-based DNA methylation panel, offering a promising strategy for the early detection of GICs.

Objective. To retrospectively analyze the results of prenatal diagnoses of noninvasive prenatal screening- (NIPS) positive pregnant women and discuss whether there is a need for chromosomal microarray analysis (CMA). Methods. The study recruited 1,019 NIPS-positive women from two prenatal diagnostic centers. Based on clinical advice, they opted for traditional karyotype analysis or CMA. Single nucleotide polymorphism array testing was performed on a commercial 750K microarray chip (Affymetrix CytoScan 750K Array). Results. Of the NIPS-positive women, 761 (74.7%) accepted the prenatal diagnosis. There were 418 (54.9%) abnormal results, and most (99.5%) were chromosome aneuploidy or structural abnormalities. Only three cases were confirmed as pathogenic copy number variation (CNVs), which were found only with CMA and not by karyotype analysis. Fifteen women were variants of uncertain significance (VUS) CNV. In addition, 300 women selected opted for both karyotype analysis and CMA for prenatal diagnosis: in 275 (91.7%) cases, the results of the two modalities were consistent, while in the remaining 25, they were not. In three cases, the additional positive results obtained with CMA were potentially clinically significant. Conclusions. CMA may not be useful for many women positive for trisomy 21/18/13 based on NIPS results, because traditional karyotype analysis can identify most problems. However, it can yield important additional findings in women positive for fetal sex chromosome aneuploidy (SCA). Further clinical studies are needed to confirm these findings.