Abstract
Background S100 family genes exclusively encode at least 20 calcium-binding proteins, which possess a wide spectrum of intracellular and extracellular functions in vertebrates. Multiple lines of evidences suggest that dysregulated S100 proteins are associated with human malignancies including colorectal cancer (CRC). However, the diverse expression patterns and prognostic roles of distinct S100 genes in CRC have not been fully elucidated. Methods In the current study, we analyzed the mRNA expression levels of S100 family genes and proteins and their associations with the survival of CRC patients using the Oncomine analysis and GEPIA databases. Expressions and mutations of S100 family genes were analyzed using the cBioPortal, and protein-protein interaction (PPI) networks of S100 proteins and their mutation-related coexpressed genes were analyzed using STRING and Cytoscape. Results We observed that the mRNA expression levels of S100A2, S100A3, S100A9, S100A11, and S100P were higher and the level of S100B was lower in CRC tissues than those in normal colon mucosa. A high S100A10 levels was associated with advanced-stage CRC. Results from GEPIA database showed that highly expressed S100A1 was correlated with worse overall survival (OS) and disease-free survival (DFS) and that overexpressions of S100A2 and S100A11 were associated with poor DFS of CRC, indicating that S100A1, S100A2, and S100A11 are potential prognostic markers. Unexpectedly, most of S100 family genes showed no significant prognostic values in CRC. Conclusions Our findings, though still need to be ascertained, offer novel insights into the prognostic implications of the S100 family in CRC and will inspire more clinical trials to explore potential S100-targeted inhibitors for the treatment of CRC.
Highlights
The S100 family, with a common Ca 2+-binding motif, EFhand, contains a group of low molecular weight acidic polypeptides (M r between 9 and 14 kDa) [1], of which more than 20 S100 proteins are encoded in the human genome [2].The S100 proteins appear to be involved in a multitude of biological processes, including calcium homeostasis, cell growth, invasion and motility, apoptosis, protein phosphorylation, chemotaxis, and inflammation [1,2,3]
Despite considerable improvements in the diagnosis and treatment of colorectal cancer (CRC), many patients are diagnosed at advanced stages or relapse, which is associated with a poor prognosis for survival
We imported 21 genes in the S100 family reported by Anne et al in the Oncomine database and compare their expression levels between the normal and cancerous CRC
Summary
The S100 family, with a common Ca 2+-binding motif, EFhand, contains a group of low molecular weight acidic polypeptides (M r between 9 and 14 kDa) [1], of which more than 20 S100 proteins are encoded in the human genome [2].The S100 proteins appear to be involved in a multitude of biological processes, including calcium homeostasis, cell growth, invasion and motility, apoptosis, protein phosphorylation, chemotaxis, and inflammation [1,2,3]. Despite considerable improvements in the diagnosis and treatment of CRC, many patients are diagnosed at advanced stages or relapse, which is associated with a poor prognosis for survival. Multiple lines of evidences suggest that dysregulated S100 proteins are associated with human malignancies including colorectal cancer (CRC). We analyzed the mRNA expression levels of S100 family genes and proteins and their associations with the survival of CRC patients using the Oncomine analysis and GEPIA databases. Results from GEPIA database showed that highly expressed S100A1 was correlated with worse overall survival (OS) and disease-free survival (DFS) and that overexpressions of S100A2 and S100A11 were associated with poor DFS of CRC, indicating that S100A1, S100A2, and S100A11 are potential prognostic markers
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