A Liquid Biopsy Assay of Exosomal miRNA for Non-invasive Identification of Lymph Node Metastasis in Early Gastric...

Additional surgical resection is required to achieve curative treatment in patients with early gastric cancer (EGC) due to the potential risk for lymph node metastasis (LNM) after pathological analysis; however, LNM is estimated to occur in approximately 10% of patients with high-risk EGC. In this study, we investigated a blood-based liquid biopsy assay of exosomal microRNA (miRNA) for the non-invasive detection of LNM in patients with high-risk EGC.

Two genome-wide miRNA expression profiling datasets [GSE164174 and The Cancer Genome Atlas (TCGA)] were analyzed to prioritize biomarkers in pretreatment plasma samples from clinical training and validation cohorts of GC patients. An integrated exosomal miRNA panel was developed and a risk stratification model combining the miRNA panel with clinical risk factors was established.

Using comprehensive expression profiling of public datasets, we identified a transcriptomic panel of four miRNAs (miR-34b, miR-130a, miR-375, and miR-627) that robustly identified patients with LNM [area under the curve (AUC) 0.86, 95% confidence interval (CI) 0.77-0.92]. We assessed panel performance in a training cohort (AUC 0.86, 95% CI 0.67-0.96) and validated it in an independent validation cohort (AUC 0.83, 95% CI 0.68-0.94). Our risk stratification model was more accurate than the panel and was an independent predictor of LNM identification (AUC 0.94).

A novel, non-invasive, liquid biopsy-based method for patients with EGC may predict those conventionally classified as high-risk patients with LNM who are unlikely to benefit from surgical resection.