Single Patient Classifier Assay, Microsatellite Instability, and Epstein-Barr Virus Status Predict Clinical Outcomes in Stage II/III Gastric Cancer: Results from CLASSIC Trial

Purpose: Clinical implications of single patient classifier (SPC) and microsatellite instability (MSI) in stage II/III gastric cancer have been reported.We investigated SPC and the status of MSI and Epstein-Barr virus (EBV) as combinatory biomarkers to predict the prognosis and responsiveness of adjuvant chemotherapy for stage II/III gastric cancer.Materials and Methods: Tumor specimens and clinical information were collected from patients enrolled in CLASSIC trial, a randomized controlled study of capecitabine plus oxaliplatin-based adjuvant chemotherapy.The results of nine-gene based SPC assay were classified as prognostication (SPC-prognosis) and prediction of chemotherapy benefit (SPC-prediction).Five quasimonomorphic mononucleotide markers were used to assess tumor MSI status.EBV-encoded small RNA in situ hybridization was performed to define EBV status.Results: There were positive associations among SPC, MSI, and EBV statuses among 586 patients.In multivariate analysis of disease-free survival, SPC-prognosis [hazard ratio (HR): 1.879 (1.101-3.205),2.399 (1.415-4.067),p=0.003] and MSI status (HR: 0.363, 95% confidence interval: 0.161-0.820,p=0.015) were independent prognostic factors along with age, Lauren classification, TNM stage, and chemotherapy.Patient survival of SPC-prognosis was well stratified regardless of EBV status and in microsatellite stable (MSS) group, but not in MSI-high group.Significant survival benefit from adjuvant chemotherapy was observed by SPC-Prediction in MSS and EBV-negative gastric cancer.Conclusion: SPC, MSI, and EBV statuses could be used in combination to predict the prognosis and responsiveness of adjuvant chemotherapy for stage II/III gastric cancer.