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

Hatthakarnkul, P. et al. (2023) Protein expression of S100A2 reveals it association with patient prognosis and immune infiltration profile in colorectal cancer. Journal of Cancer, 14(10), pp. 1837-1847. (doi: 10.7150/jca.83910) (PMID:37476187) (PMCID:PMC10355195)

Abstract

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 respectively).

• Item Type: Articles
• Additional Information: The multiplex staining and imaging were funded by the Mazumdar-Shaw chair fund and UKRI: Enabling integrated diagnostics for early detection: 42497: Integrated Technologies for Improved Polyp Surveillance (INCISE). The TSP and KM scores were funded by MRC transitional fellowship (MR/R502327/1), a studentship to Kathryn A. F. Pennel. The TempO-Seq data and analysis was funded by Cancer Research UK Scotland Centre (CTRQQR-2021\100006).
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Matly, Mrs Amna and Pennel, Miss Kathryn and Le Quesne, Professor John and Ammar, Dr Aula and Hay, Dr Jennifer and Quinn, Dr Jean and Edwards, Professor Joanne and Hatthakarnkul, Phimmada and McMillan, Professor Donald and Alexander, Peter and Lynch, Dr Gerard and Van Wyk, Dr Hester
• Authors: Hatthakarnkul, P., Ammar, A., Pennel, K. A.F., Officer-Jones, L., Cusumano, S., Quinn, J. A., Matly, A. A. M., Alexander, P. G., Hay, J., Andersen, D., Lynch, G., Van Wyk, H. C., Maka, N., McMillan, D. C., Le Quesne, J., Thuwajit, C., and Edwards, J.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Journal of Cancer
• Publisher: Ivyspring International Publisher
• ISSN: 1837-9664
• ISSN (Online): 1837-9664
• Copyright Holders: Copyright © 2023 The Authors
• First Published: First published in Journal of Cancer 14(10):1837-1847
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
313949		National Productivity Investment Fund Studentships	George Baillie	Medical Research Council (MRC)	MR/R502327/1	MVLS - Graduate School