Department of Clinical Laboratory Medicine, Fujian Medical University Union Hospital, Fuzhou 350000, China.
Department of Clinical Laboratory Medicine, Fujian Provincial Hospital, Fuzhou 350001, China.
Biomed Res Int. 2020 Nov 26;2020:4746929. doi: 10.1155/2020/4746929. eCollection 2020.
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.
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.
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.
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.
S100 家族基因专门编码至少 20 种钙结合蛋白，这些蛋白在脊椎动物中具有广泛的细胞内和细胞外功能。多条证据表明，失调的 S100 蛋白与包括结直肠癌（CRC）在内的人类恶性肿瘤有关。然而，不同 S100 基因在 CRC 中的表达模式和预后作用尚未完全阐明。
在本研究中，我们使用 Oncomine 分析和 GEPIA 数据库分析了 S100 家族基因的 mRNA 表达水平及其与 CRC 患者生存的关系。使用 cBioPortal 分析了 S100 家族基因的表达和突变，使用 STRING 和 Cytoscape 分析了 S100 蛋白的蛋白质-蛋白质相互作用（PPI）网络及其突变相关的共表达基因。
我们观察到，与正常结肠黏膜相比，CRC 组织中 S100A2、S100A3、S100A9、S100A11 和 S100P 的 mRNA 表达水平较高，而 S100B 的水平较低。高水平的 S100A10 与 CRC 晚期有关。GEPIA 数据库的结果表明，S100A1 高表达与总体生存（OS）和无病生存（DFS）较差相关，而 S100A2 和 S100A11 的过表达与 CRC 的 DFS 不良相关，表明 S100A1、S100A2 和 S100A11 是潜在的预后标志物。出乎意料的是，S100 家族的大多数基因在 CRC 中没有显示出显著的预后价值。
尽管我们的发现仍需要进一步证实，但为 S100 家族在 CRC 中的预后意义提供了新的见解，并将激发更多的临床试验来探索潜在的 S100 靶向抑制剂用于 CRC 的治疗。
