Disparity in the occurrence of EMT subtype gastric tumours with a prevalence in Indian cohorts

Objectives: Among cancer-related deaths, gastric cancer ranks third across the globe. Classification of gastric cancer by the Asian Cancer Research Group (ACRG) is a promising approach and is expected to pave the way for improved diagnosis and to evolve targeted therapeutic strategies. We explored the possibility of using ACRG subtype-specific gene sets to probe the mRNA expression profiles of gastric tumours to classify them into ACRG subtypes. Material and Methods: Thirteen cohorts of gastric tumours, including one in-house cohort from gene expression omnibus (GEO), were investigated. Subtype-specific and pathway-specific gene sets were analysed by Z-score-based computing of cumulative gene expression. Hierarchical clustering of the samples was performed based on the subtype-specific gene sets for all the cohorts and visualised as a heat map. Sensitivity and specificity were calculated for the Z-score-based assignment of both epithelial-mesenchymal transition (EMT) and microsatelliteinstable (MSI) subtypes. Results: Thirteen cohorts of gastric tumours were analysed for the prevalence of different subtypes, and the analysis revealed that Indian cohorts record a high prevalence of the EMT subtype. Further, for the first time, the co-occurrence of subtypes in individual tumour samples was also observed. Co-occurrence of EMT and MSI was found to be predominant in gastric tumours. Conclusion: The observed co-occurrence of subtypes warrants combinatorial therapeutics for gastric cancer. The disparity in the occurrence of subtypes reiterates the need for population-wide studies, implementation of molecular classification, and moving toward precision medicine.