Abstract
Immunotherapy is becoming a promising strategy for treating diverse cancers. However, it benefits only a selected group of gastric cancer (GC) patients since they have highly heterogeneous immunosuppressive microenvironments. Thus, a more sophisticated immunological subclassification and characterization of GC patients is of great practical significance for mRNA vaccine therapy. This study aimed to find a new immunological subclassification for GC and further identify specific tumor antigens for mRNA vaccine development. First, deep autoencoder (AE)-based clustering was utilized to construct the immunological profile and to uncover four distinct immune subtypes of GC, labeled as Subtypes 1, 2, 3, and 4. Then, in silico prediction using machine learning methods was performed for accurate discrimination of new classifications with an average accuracy of 97.6%. Our results suggested significant clinicopathology, molecular, and immune differences across the four subtypes. Notably, Subtype 4 was characterized by poor prognosis, reduced tumor purity, and enhanced immune cell infiltration and activity; thus, tumor-specific antigens associated with Subtype 4 were identified, and a customized mRNA vaccine was developed using immunoinformatic tools. Finally, the influence of the tumor microenvironment (TME) on treatment efficacy was assessed, emphasizing that specific patients may benefit more from this therapeutic approach. Overall, our findings could help to provide new insights into improving the prognosis and immunotherapy of GC patients.