High expression of S100A2 predicts poor prognosis in patients with endometrial carcinoma

Abstract

Background S100A2, a member of the S100 protein family, is abnormally expressed and plays a vital role in multiple cancers. However, little is known about the clinical significance of S100A2 in endometrial carcinoma. Methods Clinicopathological data were obtained from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), Gene Expression Omnibus (GEO), and Clinical Proteomic Tumor Analysis Consortium (CPTAC). First, the expression and prognostic value of different S100 family members in endometrial carcinoma were evaluated. Subsequently, the Kaplan–Meier plotter and Cox regression analysis were used to assess the prognostic significance of S100A2, while the association between S100A2 expression and clinical characteristics in endometrial carcinoma was also analyzed using logistic regression. A receiver operating characteristic (ROC) curve and a nomogram were constructed. The putative underlying cellular mechanisms were explored using Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and gene set enrichment analysis (GSEA). Results Our results revealed that S100A2 expression was significantly higher in endometrial carcinoma tissue than in non-cancerous tissue at both the mRNA and protein levels. Analysis of Kaplan–Meier plotter data revealed that patients with high S100A2 expression had shorter overall survival (OS) and disease specific survival (DSS) compared with those of patients with low S100A2 expression. Multivariate Cox analysis further confirmed that high S100A2 expression was an independent risk factor for OS in patients with endometrial carcinoma. Other clinicopathologic features found to be related to worse prognosis in endometrial carcinoma included age, clinical stage, histologic grade, and tumor invasion. Importantly, ROC analysis also confirmed that S100A2 has a high diagnostic value in endometrial carcinoma. KEGG enrichment analysis and GSEA revealed that the estrogen and IL-17 signaling pathways were significantly upregulated in the high S100A2 expression group, in which estrogen response, JAK-STAT3, K-Ras, and TNFα/NF-κB were differentially enriched. Conclusions S100A2 plays an important role in endometrial carcinoma progression and may represent an independent diagnostic and prognostic biomarker for endometrial carcinoma.

The roles and clinical applications of interleukins in endometrial carcinoma

“…For the IL-17 levels in serum, Brooks et al (44) reported no significant difference between EC patients and women without cancer, but this study has an obvious limitation of sample size that it only included 12 EC patients and 10 controls. By the way, it is worth noting that IL-17 signaling pathway was upregulated and enriched in EC supported by recent studies (92)(93)(94)(95). Besides, the serum level of IL-3 showed no difference between EC patients and healthy controls (96).…”

High MICAL-L2 expression and its role in the prognosis of colon adenocarcinoma

“…Enriched pathways were determined using Gene Ontology (GO) [ 21 , 22 ], KEGG [ 23 – 25 ], and GSEA [ 26 , 27 ]. In the KEGG analysis, genes were determined to be differentially expressed based on a log2 fold-change of > 1.0 and an adjusted P -value < 0.05 ( www.kegg.jp/kegg/kegg1.html ), as previously reported [ 28 ]. “GSEA is a computational method that determines whether an a priori defined set of genes shows statistically significant, concordant differences between two biological states” [ 26 , 27 ].…”

Influence of S100A2 in Human Diseases

“…S100A2 expression is upregulated in endometrial carcinoma tissues in vivo [ 70 ]. Patients with endometrial carcinoma with high S100A2 expression exhibit poor overall survival and disease-specific survival in vivo [ 70 ].…”