Bioinformatics analyses for the identification of tumor antigens and immune subtypes of gastric adenocarcinoma

Abstract

Background: Although mRNA vaccines have been effective against multiple cancers, their efficacy against stomach adenocarcinoma (STAD) remains undefined. Immunotyping can indicate the comprehensive immune status in tumors and their immune microenvironment, which is closely associated with therapeutic response and vaccination potential. The aim of this study was to identify potential antigens in STAD for mRNA vaccine development, and further distinguish immune subtypes of STAD to construct an immune landscape for selecting suitable patients for vaccination.Methods: The gene expression and clinicopathological features of patients with gastric cancer were downloaded from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression Program (GTEx). 729 samples from GSE66229 and GSE84437 were downloaded through GEO and were used as the validation cohorts. Differential gene expression, genetic alterations and prognosis were analyzed using the R package, cBioPortal program and Kaplan-Meier. The relationship between tumor antigens and immune cells was evaluated and plotted by TIMER. ConsensusClusterPlus was used for consistency matrix construction and data clustering, and graph learning-based dimensional reduction was used to depict immune landscape. WGCNA was used to estimate the relationship between the color modules and immune subtypes.Results: Two overexpressed and mutated tumor antigens associated with poor prognosis and infiltration of antigen presenting cells were identified in STAD, including RAI14 and NREP. The immune subtypes showed distinct molecular, cellular and clinical characteristics. IS1 and IS2 exhibited immune-activated phenotypes and correlated to better survival compared to IS3, while IS3 tumors was immunologically cold. Immunogenic cell death modulators, immune checkpoints, and CA125, and CEA were also differentially expressed among the three immune subtypes. Finally, the immune landscape of STAD showed a high degree of heterogeneity between individual patients.Conclusion: RAI14 and NREP are potential antigens for developing anti-STAD mRNA vaccine, and patients with IS1 and IS3 tumors may be suitable for vaccination.

Structural variants in the Epb41l4a locus: TAD disruption and Nrep gene misregulation as hypothetical drivers of neurodevelopmental outcomes

“…Despite not belonging to any recognized protein family or having signature motifs indicating function, it contains three PEST-like domains, which are subject to rapid degradation via the ubiquitin–proteasome system 18 – 20 . NREP is known to enhance cell proliferation 19 and migration 16 during vascularization and wound healing 21 – 24 and is involved in the development of various cancer types 25 – 28 . Within the nervous system, NREP governs neurite outgrowth by managing Rho kinase activity.…”

Molecular characteristics, potential mechanisms and prognostic gene model of younger female patients with gastric cancer

“…Most of the genes in the prognostic gene model have been reported to be associated with cancer development. NREP played an important role in the progression of GC through diverse mechanisms, such as epithelial-mesenchymal transition activation, cancer-associated broblasts activation, actin cytoskeleton remodeling, and M2 macrophage in ltration, and its expression was powerfully associated with T stage and histologic grade [42][43][44]. KRT17 could promote the proliferation, migration, and invasion of GC cells, and its expression was positively correlated with the TMN stage, lymphatic metastasis, depth of invasion and vascular invasion [45][46][47].…”

Identification of colon adenocarcinoma necroptosis subtypes and tumor antigens for the development of mRNA vaccines

“…Therefore, further research and development of new mRNA vaccine technologies are needed to overcome the challenges of various diseases. For unexplored applications of mRNA in a particular disease, researchers could utilize high-throughput technologies and bioinformatics methods to find suitable targets and antigens and continuously optimize mRNA vaccine technology to improve its efficacy and safety [ 38 ].…”