Search

Background: Patients with gastric and gastroesophageal junction adenocarcinomas (G-GEJ ACs) face poor outcomes. Thus sensitive biomarkers for improved clinical management are highly warranted. Detection of circulating tumor DNA (ctDNA) using DNA methylation biomarkers is a highly sensitive approach for cancer detection and management. Here, we explored the potential of a tumor-agnostic test targeting DNA methylation to detect ctDNA in patients with resectable and advanced G-GEJ ACs. Material and methods: A tumor-agnostic digital PCR test—TriMeth—targeting the gastrointestinal cancer-specific methylated genes C9orf50, KCNQ5, and CLIP4 was carried out on a total of 131 study patients. DNA from surgical tumor specimens of 29 patients with G-GEJ ACs and plasma cell-free DNA from 52 patients with advanced and resectable G-GEJ ACs, and from 50 healthy controls, were analyzed. Results: Methylated tumor DNA was detected by TriMeth in all of the surgical tumor specimens (29/29, 100%). Furthermore, TriMeth detected ctDNA in plasma from 31/52 (60%) patients with G-GEJ AC, including in 13/17 (76%) advanced cases, and 18/35 (51%) resectable cases. ctDNA was not detected in healthy controls (0/50, 0%). Conclusions: This study demonstrates that TriMeth may hold potential as a biomarker for identifying ctDNA in patients with G-GEJ ACs. The study sets the scene for ongoing larger clinical studies investigating the performance of TriMeth in different clinical settings.

Introduction. Esophageal adenocarcinoma develops from areas of intestinal metaplasia in Barrett’s esophagus, similar to how intestinal metaplasia transforms into gastric adenocarcinomas in the stomach. Atypia with intraepithelial neoplasia is difficult to distinguish from reactive and regenerative changes, especially in erosive mucosa of the esophagus. Observation of patients with Barrett’s esophagus allows the identification of adenocarcinoma in the earlier, more curable stages in many patients.The aim of our study was to study the prospects of using a classifier based on miRNA profiling in histological samples of Barrett’s esophagus to determine the risk of malignancy and treatment tactics.Material and Methods. In this study, 119 samples of archival histological material in the form of paraffin blocks were used: 89 samples of gastric mucosa with dysplasia and 30 samples of Barrett’s esophagus. The expression level of miRNA-145-5p, -150-5p, -20a-5p, -21-5p,-31-5p,-34a-5p,-375 was determined using real-time RT-PC R. Samples were stratified into different groups using the C-RT decision tree algorithm.Results. 26.7 % of Barrett’s esophagus samples were classified by expression of the proposed miRNAs as cancer, which may indicate a potential development of a malignant tumor in the mucosa of the esophagus when morphological changes have not yet been found.

Background The microRNAs (miRNAs) have been validated as prognostic markers in many cancers. Here, we aimed at developing a miRNA-based signature for predicting the prognosis of esophagus adenocarcinoma (EAC). Methods The RNA-sequencing data set of EAC was downloaded from The Cancer Genome Atlas (TCGA). Eighty-four patients with EAC were classified into a training set and a test set randomly. Using univariate Cox regression analysis and the least absolute shrinkage and selection operator (LASSO), we identified prognostic factors and constructed a prognostic miRNA signature. The accuracy of the signature was evaluated by the receiver operating characteristic (ROC) curve. Result In general, in the training set, six miRNAs (hsa-mir-425, hsa-let-7b, hsa-mir-23a, hsa-mir-3074, hsa-mir-424 and hsa-mir-505) displayed good prognostic power as markers of overall survival for EAC patients. Relative to patients in the low-risk group, those assigned to the high-risk group according to their risk scores of the designed miRNA model displayed reduced overall survival. This 6-miRNA model was validated in test and entire set. The area under curve (AUC) for ROC at 3 years was 0.959, 0.840, and 0.868 in training, test, and entire set, respectively. Molecular functional analysis and pathway enrichment analysis indicated that the target messenger RNAs associated with 6-miRNA signature were closely related to several pathways involved in carcinogenesis, especially cell cycle. Conclusion In summary, a novel 6-miRNA expression-based prognostic signature derived from the EAC data of TCGA was constructed and validated for predicting the prognosis of EAC.