Abstract
BackgroundS100A2, 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.MethodsClinicopathological 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).ResultsOur 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.ConclusionsS100A2 plays an important role in endometrial carcinoma progression and may represent an independent diagnostic and prognostic biomarker for endometrial carcinoma.
Highlights
S100A2, a member of the S100 protein family, is abnormally expressed and plays a vital role in multiple cancers
High S100A2 expression is correlated with clinicopathologic features in patients with endometrial carcinoma S100A2 was found high expressed in the GSE17025 and GSE39099 profiles and screened out among the six genes
The results showed that S100A2 mRNA expression levels were significantly higher in endometrial carcinoma primary tumor samples than in normal tissue (P < 0.05)
Summary
S100A2, a member of the S100 protein family, is abnormally expressed and plays a vital role in multiple cancers. Endometrial carcinoma is one of the most commonly diagnosed gynecological malignancies, with nearly 400,000 new cases reported in 2020 [1]. It comprises a group of malignant epithelial tumors that originate in the inner lining of the uterus and frequently occur in. S100A2 can bind zinc, which significantly reduces its affinity for calcium [4, 5] Upon binding of those ions, most S100 proteins undergo conformational changes, which allows them to interact with other proteins and thereby play key roles in a wide range of cellular functions. How S100 proteins affect the pathogenesis and prognosis of endometrial carcinoma remains to be determined
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