Alexander, Peter G.

Ammar, Aula

Andersen, Ditte

Cusumano, Silvia

Edwards, Joanne

Hatthakarnkul, Phimmada

Hay, Jennifer

Le Quesne, John

Lynch, Gerard

Maka, Noori

Matly, Amna Ahmed Mohemmed

McMillan, Donald C.

Officer-Jones, Leah

Pennel, Kathryn A.F.

Quinn, Jean A.

Thuwajit, Chanitra

Van Wyk, Hester C.

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&lt;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&lt;0.001, P=0.009 respectively)

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

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

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