Background: The new S100 protein family member S100A16 is functionally expressed in various cancers. This study explored the prognostic value and potential role of S100A16 in pancreatic cancer (PC).
Methods: RNA-seq and clinical data were obtained from The Cancer Genome Atlas-Pancreatic Adenocarcinoma (TCGA-PAAD) dataset to compare the expression level of S100A16 between groups. The genes co-expressed with S100A16 in TCGA-PAAD were analyzed using cBioPortal. Gene Ontology and Kyoto Encyclopedia of Genes and genomes enrichment analyses were also performed on these genes. Pathways related to S100A16 expression dysregulation were explored using gene set enrichment analysis. The Tumor Immune Estimation Resource was used to analyze the correlation between S100A16 and infiltrating immune cells. The Kaplan-Meier method and Cox analyses were used to assess the prognostic significance of S100A16 for PC.
Results: The S100A16 expression level was high in PC and increased with the degree of malignancy. The S100A16 functions in PC were mainly enriched in the immune modules, but negatively correlated with the immune activity (T-cell, cytokine, immune, co-receptor, signaling adaptor, cell adhesion molecule, chemokine, and JAK/STAT signaling) and infiltration level (T cells and macrophages). The strongest negative correlation was observed between the expression of CD8+ T cells and S100A16. Furthermore, high S100A16 expression also indicated worse overall survival and, therefore, worse prognosis of PC.
Conclusion: S100A16 is a potential independent prognostic marker and immunotherapy target for PC. Mechanistically, S100A16 potentially affects prognosis by extensive immunosuppression, including the inhibition of the anti-tumor immune response of CD8+ T cells.
Keywords: CD8+ T cells; S100A16; immune infiltration; immunosuppression; pancreatic cancer; prognostic marker.
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