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Spatial transcriptomic analysis of tumour with high and low CAIX expression in TNBC tissue samples using GeoMx™ RNA assay

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dc.contributor.authorShamis, Suad A.K.
dc.contributor.authorSavioli, Francesca
dc.contributor.authorAmmar, Aula
dc.contributor.authorAl Badran, Sara S.F.
dc.contributor.authorHatthakarnkul, Phimmada
dc.contributor.authorLeslie, Holly
dc.contributor.authorMallon, Elizabeth E.A.
dc.contributor.authorJamieson, Nigel B.
dc.contributor.authorMcMillan, Donald C
dc.contributor.authorEdwards, Joanne
dc.date.accessioned2024-01-29T09:32:43Z
dc.date.available2024-01-29T09:32:43Z
dc.date.issued2024
dc.description.abstractPurpose. 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 (pancytokeratin+) and stroma (pan-cytokeratin-). Differentially expressed genes (DEGs) with P<0.05 and log2 fold change (FC)>(±0.25 and ±0.3, for tumour and stromal compartment, respectively) 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 warrantedes
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dc.format.extent24es
dc.identifier.citationHistology and Histopathology Vol. 39, nº2 (2024)
dc.identifier.doihttps://doi.org/10.14670/HH-18-655
dc.identifier.issn0213-3911
dc.identifier.issn1699-5848
dc.identifier.urihttp://hdl.handle.net/10201/137894
dc.languageenges
dc.publisherUniversidad de Murcia, Departamento de Biologia Celular e Histiologiaes
dc.relationSin financiación externa a la Universidades
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectBreast canceres
dc.subjectCAIXes
dc.subjectHypoxia gene expressiones
dc.subjectNanostring nCounter techonology transcriptomicses
dc.subjectHIF-1αes
dc.subjectApoptosises
dc.subjectBCL2es
dc.subjectInfiltrating macrophageses
dc.subjectCD68es
dc.subjectLymphocyteses
dc.subjectCD3es
dc.subjectStromal microenvironmentes
dc.subject.otherCDU::6 - Ciencias aplicadas::61 - Medicina::616 - Patología. Medicina clínica. Oncologíaes
dc.titleSpatial transcriptomic analysis of tumour with high and low CAIX expression in TNBC tissue samples using GeoMx™ RNA assayes
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
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Histology and histopathology Vol.39, nº2 (2024)