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

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).
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High expression of S100A2 predicts poor prognosis in patients with endometrial carcinomaZhangetal. BMC Cancer (2022) 22:77https://doi.org/10.1186/s12885-022-09180-5 RESEARCH Open AccessHigh expression ofS100A2 predictspoor prognosis inpatients withendometrialcarcinomaQinzhenZhang1†, TianxiangXia2†, ChenxiangQi2, JunDu2*and ChunpingYe3*  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 Expres- sion (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. Sub- sequently, 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 fea- tures 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 sig- nificantly 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 inde- pendent diagnostic and prognostic biomarker for endometrial carcinoma. Keywords:  S100A2, Overall survival, Prognosis, Endometrial carcinoma, Bioinformatics*Correspondence: dujun@njmu.edu.cn; ycp12@126.com Background† Qinzhen Zhang and Tianxiang Xia contributed equally to this paper. Endometrial carcinoma is one of the most commonly2 Department ofPhysiology, Nanjing Medical University, 101 Longmian diagnosed gynecological malignancies, with nearlyAvenue, Jiangning District, 211166Nanjing, Jiangsu, China3 Department ofObstetrics andGynecology, Nanjing Maternity andChild 400,000 new cases reported in 2020 [1]. It comprises aHealth Care Hospital, Women’s Hospital ofNanjing Medical University, 123 group of malignant epithelial tumors that originate inMochou Road, 210004Nanjing, Jiangsu, China the inner lining of the uterus and frequently occur inFull list of author information is available at the end of the article © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://​creat​iveco​mmons.​org/​licen​ses/​by/4.​0/. The Creative Commons Public Domain Dedication waiver (http://​creat​iveco​ mmons.​org/​publi​cdoma​in/​zero/1.​0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.Zhangetal. BMC Cancer (2022) 22:77 Page 2 of 11perimenopausal and postmenopausal women. The inci- Genes and Genomes (KEGG) pathway enrichment analy-dence of endometrial carcinoma has shown a gradual sis. Our results suggested that S100A2 may be a promis-increase over recent years concomitant with an improve- ing diagnostic and progno ...