Shamis, S. A. K., Savioli, F., Ammar, A. , Al-Badran, S. S.F., Hatthakarnkul, P. , Leslie, H. , Mallon, E., Jamieson, N. B. , McMillan, D. C. and Edwards, J. (2024) Spatial transcriptomic analysis of tumour with high and low CAIX expression in TNBC tissue samples using GeoMx™ RNA assay. Histology and Histopathology: Cellular and Molecular Biology, 39, pp. 177-200. (doi: 10.14670/HH-18-655) (PMID:37681672)
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Abstract
Purpose. Prognostic significance and gene signatures associated with carbonic anhydrase IX (CAIX) was investigated in triple negative breast cancer (TNBC) patients. Methods. Immunohistochemistry (IHC) for CAIX was performed in tissue microarrays (TMAs) of 136 TNBC patients.In a subset of 52 patients Digital Spatial Profiler (DSP) was performed in tumour (pan-cytokeratin+) and stroma (pan-cytokeratin-). Differentially expressed genes (DEGs) with P<0.05 and fold change ≥1 or ≤-1 were identified. Four genes were validated at the protein level. Result. Cytoplasmic CAIX expression was independently associated with poor recurrence free survival in TNBC patients [hazard ratio (HR)=6.59, 95% confidence interval (CI): 1.47-29.58, P=0.014]. DEG analysis identified 4 up-regulated genes (CD68, HIF1A, pan-melanocyte, and VSIR) in the tumour region and 9 down-regulated genes in the stromal region (CD86, CD3E, MS4A1, BCL2, CCL5, NKG7, PTPRC, CD27, and FAS) when low versus high CAIX expression was explored. Employing IHC, high CD68 and HIF-1α was associated with poorer prognosis and high BCL2 and CD3 was associated with good prognosis. Conclusions. DSP technology identified DEGs in TNBC. Selected genes validated by IHC showed involvement of CD3 and BCL2 expression within stroma and HIF-1α, and CD68 expression within tumour. However, further functional analysis is warranted.
| Item Type: | Articles |
|---|---|
| Additional Information: | This research was funded by Libyan government and Libyan Cultural Affairs Bureau (Grant no. AA274-518-54090). Funding CRUK Clinician Scientist Award (C55370/A25813; N.J). |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Jamieson, Professor Nigel and Al-Badran, Ms Sara and Mallon, Dr Elizabeth and Ammar, Dr Aula and Leslie, Ms Holly and Edwards, Professor Joanne and Savioli, Francesca and Hatthakarnkul, Phimmada and McMillan, Professor Donald and Shamis, Suad Ahmad Khalifa |
| Authors: | Shamis, S. A. K., Savioli, F., Ammar, A., Al-Badran, S. S.F., Hatthakarnkul, P., Leslie, H., Mallon, E., Jamieson, N. B., McMillan, D. C., and Edwards, J. |
| College/School: | College of Medical Veterinary and Life Sciences 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: | Histology and Histopathology: Cellular and Molecular Biology |
| Publisher: | Universidad de Murcia |
| ISSN: | 0213-3911 |
| ISSN (Online): | 1699-5848 |
| Published Online: | 31 July 2023 |
| Copyright Holders: | Copyright © The Author(s) 2024 |
| First Published: | First published in Histology and Histopathology: Cellular and Molecular Biology 39:177-200 |
| Publisher Policy: | Reproduced under a Creative Commons license |
| Data DOI: | 10.5525/gla.researchdata.1333 |
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