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

Hatthakarnkul, Phimmada; Ammar, Aula; Pennel, Kathryn A. F.; Officer-Jones, Leah; Cusumano, Silvia; Quinn, Jean A.; Matly, Amna Ahmed Mohemmed; Alexander, Peter G.; Hay, Jennifer; Andersen, Ditte; Lynch, Gerard; van Wyk, Hester C.; Maka, Noori; McMillan, Donald C.; Le Quesne, John; Thuwajit, Chanitra; Edwards, Joanne

doi:10.7150/jca.83910

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J Cancer 2023; 14(10):1837-1847. doi:10.7150/jca.83910 This issue Cite

Research Paper

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

Phimmada Hatthakarnkul^1,2, Aula Ammar¹, Kathryn A. F. Pennel¹, Leah Officer-Jones⁶, Silvia Cusumano⁶, Jean A. Quinn¹, Amna Ahmed Mohemmed Matly¹, Peter G. Alexander³, Jennifer Hay⁵, Ditte Andersen⁷, Gerard Lynch¹, Hester C. van Wyk³, Noori Maka³, Donald C. McMillan³, John Le Quesne^6,1, Chanitra Thuwajit⁴, Joanne Edwards^1✉

1. School of Cancer Sciences, University of Glasgow, Wolfson Wohl Cancer Research Centre, Garscube Estate, Glasgow, United Kingdom.
2. Biomedical Science Program, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
3. School of Medicine, University of Glasgow, Glasgow Royal Infirmary, Alexandria Parade, Glasgow, United Kingdom.
4. Department of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
5. Glasgow Tissue Research Facility, University of Glasgow, Queen Elizabeth University Hospital, Glasgow, United Kingdom.
6. Cancer Research UK Beatson Institute, Garscube Estate, Glasgow, United Kingdom.
7. BioClavis Ltd, Glasgow, United Kingdom.

Citation:

Hatthakarnkul P, Ammar A, Pennel KAF, Officer-Jones L, Cusumano S, Quinn JA, Matly AAM, Alexander PG, Hay J, Andersen D, Lynch G, van Wyk HC, Maka N, McMillan DC, Le Quesne J, Thuwajit C, Edwards J. Protein expression of S100A2 reveals it association with patient prognosis and immune infiltration profile in colorectal cancer. J Cancer 2023; 14(10):1837-1847. doi:10.7150/jca.83910. https://www.jcancer.org/v14p1837.htm

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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).

Conclusion: Our finding demonstrates a prognostic value of S100A2 together with the correlation with immune infiltration in CRC.

Keywords: S100A2, inflammatory, colorectal cancer

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APA

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., Edwards, J. (2023). Protein expression of S100A2 reveals it association with patient prognosis and immune infiltration profile in colorectal cancer. Journal of Cancer, 14(10), 1837-1847. https://doi.org/10.7150/jca.83910.

ACS

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.; Edwards, J. Protein expression of S100A2 reveals it association with patient prognosis and immune infiltration profile in colorectal cancer. J. Cancer 2023, 14 (10), 1837-1847. DOI: 10.7150/jca.83910.

NLM

CSE

Hatthakarnkul P, Ammar A, Pennel KAF, Officer-Jones L, Cusumano S, Quinn JA, Matly AAM, Alexander PG, Hay J, Andersen D, Lynch G, van Wyk HC, Maka N, McMillan DC, Le Quesne J, Thuwajit C, Edwards J. 2023. Protein expression of S100A2 reveals it association with patient prognosis and immune infiltration profile in colorectal cancer. J Cancer. 14(10):1837-1847.

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