Comprehensive analysis of the prognosis of S100 family members and their relationship with tumor-infiltrating immune cells in human pancreatic adenocarcinoma

Abstract

S100 family members (S100s) are small molecular EF hand calcium binding proteins and widely expressed in many tissues and organs. S100s are shown to be biomarkers of disease progression and prognosis in various types of cancers. Nevertheless, the expression patterns, function, and prognostic values of S100s and its association with tumor-infiltrating immune cells in pancreatic adenocarcinoma (PAAD) patients have not been systematically clarified. We explored the expression and roles of the entire 20 S100s in PAAD patients by using the following public databases: Oncomine, gene expression profiling interactive analysis, cBioPortal, Metascape, search tool for recurring instances of neighboring genes, Tumor IMmune Estimation Resource, and GeneMANIA. The S100A2/A3/A4/A6/A8/A9/A10/A11/A13/A14/A16/B/P mRNA expressions were significantly upregulated in PAAD patients. The mRNA expression of S100A3/A4/A5/A6/A10/A11/A14/A16/Z were significantly negatively related with the tumor stage in PAAD patients. We found that the S100A2/A3/A5/A10/A11/A14/A16 were significantly correlated with poor overall survival, whereas the increased levels of S100A1/B/G/Z were strongly associated with good overall survival. We found significant correlations among S100s and tumor-infiltrating immune cells. Cox proportional risk models revealed that B cells, Dendritic cells and S100A1/A5/A6/A8/A9/A13/A14 were significantly related with outcomes in PAAD patients. These results suggest that S100A2/A3/A10/A11/A14/A16 may serve as new diagnostic and prognostic biomarkers for PAAD patients and provide new clues for immunotherapy in PAAD patients.