Browsing by Author "Alexander P.G."

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    Protein expression of S100A2 reveals it association with patient prognosis and immune infiltration profile in colorectal cancer
    (2023-01-01) 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.; Mahidol University
    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.
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    The relationship between the Glasgow Microenvironment Score and markers of epithelial-mesenchymal transition in TNM II-III colorectal cancer
    (2022-09-01) Alexander P.G.; Matly A.A.M.; Jirapongwattana N.; Pennel K.A.F.; van Wyk H.C.; McMillan D.C.; Horgan P.G.; Roxburgh C.S.D.; Thuwajit C.; Roseweir A.K.; Quinn J.; Park J.H.; Edwards J.; Mahidol University
    Recently published work on the Glasgow Microenvironment Score (GMS) demonstrated its relevance as a biomarker in TNM II-III colorectal cancer (CRC). Epithelial-mesenchymal transition (EMT) markers in CRC have also shown promise as prognostic biomarkers. This study aimed to assess the relationship between GMS and markers of EMT in stage II-III CRC. A previously constructed tissue microarray of CRC tumors resected between 2000 and 2007 from the Western Infirmary, Stobhill, and Gartnavel General Hospitals in Glasgow was used. Immunohistochemistry was performed for 5 markers of EMT: E-cadherin, β-catenin, Fascin, Snail, and Zeb1. Two-hundred and thirty-eight TNM II-III CRC with valid scores for all EMT markers and GMS were assessed. The prognostic significance of markers of EMT in this cohort and relationships between GMS and markers of EMT were determined. High cytoplasmic and nuclear β-catenin and membrane Zeb-1 were significant for worse cancer-specific survival (hazard ratio [HR] 1.67, 95% confidence interval [CI] 1.01–2.76, P <.05; HR 2.22, 95% CI 1.24–3.97, P <.01; and HR 2.00, 95% CI 1.07–3.77, P =.03, respectively). GMS 0 was associated with low membrane Fascin (P =.03), whereas membrane and cytoplasmic Fascin were observed to be highest in GMS 1, but lower in GMS 2. Nuclear β-catenin was lowest in GMS 0, but highest in GMS 2 (P =.03), in keeping with its role in facilitating EMT. Novel associations were demonstrated between GMS categories and markers of EMT, particularly β-catenin and Fascin, which require further investigation in independent cohorts.