Spatial Transcriptomics Reveal Pitfalls and Opportunities for the Detection of Rare High-Plasticity Breast Cancer Subtypes

• DOI: 10.1016/j.labinv.2023.100258
• Publication Date: 2023-10-07T15:07:30Z
• Authors: Angèle Coutant; Vincent Cockenpot; Lauriane Muller; Cyril Degletagne; Roxane Pommier; Laurie Tonon; Maude Ardin; Marie-Cécile Mich...; Christophe Caux; Marie Laurent; Anne-Pierre Morel; Pierre Saintigny; Alain Puisieux; Maria Ouzounova; Pierre Martinez
• Keywords: Gene Expression Profiling; Ubiquitin-Protein Ligases; Muscle Proteins; Breast Neoplasms; Triple Negative Breast Neoplasms; Prognosis; 3. Good health; Claudins; Humans; Female; Breast; Transcriptome; Carrier Proteins; Cell Adhesion Molecules

<h2>Abstract</h2> Breast cancer is one of the most prominent types cancers, in which therapeutic resistance a major clinical concern. Specific subtypes, such as claudin-low and metaplastic breast carcinoma (MpBC), have been associated with high nongenetic plasticity, can facilitate resistance. The similarities differences between these orthogonal identified by molecular histopathological analyses, respectively, remain insufficiently characterized. Furthermore, adequate methods to identify high-plasticity tumors better anticipate are lacking. Here, we analyzed 11 triple-negative tumors, including 3 4 MpBC, via high-resolution spatial transcriptomics. We combined pathological annotations deconvolution approaches precisely tumor spots, on performed signature enrichment, differential expression, copy number analyses. used Cancer Genome Atlas Cell Line Encyclopedia public databases for external validation expression markers. By focusing our transcriptomic analyses cells MpBC samples, bypassed negative impact stromal contamination specific markers that neither expressed other subtypes nor cells. Three (<i>BMPER</i>, <i>POPDC3</i>, <i>SH3RF3</i>) were validated encompassing bulk material stroma-free cell lines. unveiled existing signatures cancers relevant mesenchymal transdifferentiated compartments but be hindered abundant negatively impacting their applicability. Spatial constitute powerful tools could thus enhance diagnosis care rare cancers.