Reproduction of molecular subtypes of gastric adenocarcinoma by transcriptome sequencing of archival tissue

Abstract

Abstract Gastric cancer (GC) is a heterogeneous disease, so molecular classification is important for selecting the most appropriate treatment strategies for GC patients. To be applicable in the clinic, there is an urgent need for a platform that will allow screening real-life archival tissue specimens. For this purpose, we performed RNA sequencing of 50 samples from our Asian Cancer Research Group (ACRG) GC cohort to reproduce the molecular subtypes of GC using archival tissues with different platforms. We filtered out genes from the epithelial-to-mesenchymal transition (EMT) and microsatellite instability-high (MSI) signatures (coefficient ≤ 0.4) followed by the ACRG molecular subtype strategy. Overall accuracy of reproduction of ACRG subtype was 66% (33/50). Given the importance of EMT subtype in future clinical trials, we further developed the minimum number of genes (10 genes) for EMT signatures correlating highly with the original EMT signatures (correlation ≥ 0.65). Using our 10-gene model, we could classify EMT subtypes with high sensitivity (0.9576) and specificity (0.811). In conclusion, we reproduced ACRG GC subtypes using different platforms and could predict EMT subtypes with 10 genes and are now planning to use them in our prospective clinical study of precision oncology in GC.