Increased SEC23A Expression Correlates with Poor Prognosis and Immune Infiltration in Stomach Adenocarcinoma

Simple Summary: Research on the biological and molecular characteristics of stomach adenocarcinoma (STAD) is mandatory to identify molecular markers and targets for diagnosis, prognosis and therapeutic interventions. The SEC23A gene is involved in the occurrence and development of various tumor entities. However, little is known about its expression and relevance for STAD. By combining computational biology with validation on patient tissue samples, this study is the first to describe the significantly upregulated expression of SEC23A in STAD. We also identified an association with disease progression, STAD patients' prognosis, and several infiltrating immune cell types and their activity. We observed the significantly upregulated expression of SEC23A in STAD, an association with disease progression, patients' prognosis and infiltrating immune cell subsets. Thus, we propose SEC23A as an independent prognostic factor with a putative role in immune response regulation in STAD.Background: Previous studies have described that the SEC23A gene is involved in the occurrence and development of various tumor entities. However, little is known about its expression and relevance in stomach adenocarcinoma (STAD). The aim of this study was to bioinformatically analyze the role of SEC23A in STAD, followed by patient tissue sample analyses. Materials and methods: SEC23A expression levels in STAD and normal gastric tissues were analyzed in the Cancer Genome Atlas and Gene Expression Omnibus databases; results were verified in fresh clinical STAD specimens on both gene and protein expression levels. SEC23A expression correlated with survival parameters by Kaplan-Meier and multivariate Cox regression analyses. The top genes co-expressed with SEC23A were identified by gene set enrichment analysis (GSEA) using the clusterProfiler package in R. Furthermore, the R package (immunedeconv), integrating the CIBERSORT algorithm, was used to estimate immune cell infiltration levels in STAD. Results: SEC23A gene and sec23a protein expression were both significantly upregulated in STAD, and this correlated with the pT stage. Moreover, high SEC23A expression was associated with poor disease-free and overall survival of STAD patients. Cox analyses revealed that besides age and pathologic stage, SEC23A expression is an independent risk factor for STAD. GSEA indicated that SEC23A was positively associated with ECM-related pathways. In the CIBERSORT analysis, the level of SEC23A negatively correlated with various infiltrating immune cell subsets, including follicular helper T cells, Tregs, activated NK cells and myeloid dendritic cells. Finally, the expression levels of immune checkpoint-related genes, including HAVCR2 and PDCD1LG2, were significantly increased in the high SEC23A expression group. Conclusions: We observed the significantly upregulated expression of SEC23A in STAD, an association with disease progression, patients' prognosis and infiltrating immune cell subsets. Thus, we propose SEC23A as an independent prognostic factor with a putative role in immune response regulation in STAD.

Automated summary

This study is the first to describe the significantly upregulated expression of the SEC23A gene in stomach adenocarcinoma (STAD). It also identified an association with disease progression, patients' prognosis, and infiltrating immune cell types and their activity. SEC23A is proposed as an independent prognostic factor with a putative role in immune response regulation in STAD.