Protein expression of S100A2 reveals it association with patient prognosis and immune infiltration profile in colorectal cancer

作者：Phimmada Hatthakarnkul, Aula Ammar, Kathryn A.F. Pennel, Leah Officer-Jones, Silvia Cusumano, Jean A. Quinn, Amna Ahmed Mohemmed Matly, Peter G. Alexander, Jennifer R. Hay, Ditte K. Andersen, Gerard Lynch, Hester Catharina Van Wyk, Noori Maka, Donald McMillan, John P. C. Le Quesne, Chanitra Thuwajit, Joanne Edwards · 发表于：Journal of Cancer · 年份：2023 · DOI：10.7150/jca.83910 · 被引用次数：11 · 研究领域：S100 Proteins and Annexins、Ferroptosis and cancer prognosis、Biomarkers in Disease Mechanisms

Purpose: Colorectal cancer (CRC) is the third most diagnosed cancer worldwide.Despite a well-established knowledge of tumour development, biomarkers to predict patient outcomes are still required.S100 calcium-binding protein A2 (S100A2) has been purposed as a potential marker in many types of cancer, however, the prognostic value of S100A2 in CRC is rarely reported.Material and Methods: In this study, immunohistochemistry (IHC) was performed to identify the prognostic role of S100A2 protein expression in the tumour core of the tissue microarrays (TMAs) in colorectal cancer patients (n=787).Bulk RNA transcriptomic data was used to identify significant genes compared between low and high cytoplasmic S100A2 groups.Multiplex immunofluorescence (mIF) was performed to further study and confirm the immune infiltration in tumours with low and high cytoplasmic S100A2.Results: Low cytoplasmic protein expression of S100A2 in the tumour core was associated with poor survival (HR 0.539, 95%CI 0.394-0.737,P<0.001) and other adverse tumour phenotypes.RNA transcriptomic analysis showed a gene significantly associated with the low cytoplasmic S100A2 group (AKT3, TAGLN, MYLK, FGD6 and ETFDH), which correlated with tumour development and progression.GSEA analysis identifies the enriched anti-tumour and immune activity group of genes in high cytoplasmic S100A2.Additionally, mIF staining showed that high CD3+FOXP3+ and CD163+ inversely associated with low cytoplasmic S100A2 (P<0.001,P=0.009 respe...