Identification of disease-promoting stromal components by comparative proteomic and transcriptomic profiling of canine mammary tumors using laser-capture microdissected FFPE tissue

Cancer-associated stroma (CAS) profoundly influences progression of tumors including mammary carcinoma (mCA). Canine simple mCA represent relevant models human mCA, notably also with respect to CAS. While transcriptomic changes in CAS are well described, it remains unclear what extent these translate the protein level. Therefore, we sought gain insight into proteomic and compare them same tissue. To this end, analyzed matched normal using laser-capture microdissection (LCM) LC-MS/MS a cohort 14 formalin-fixed paraffin embedded (FFPE) canine mCAs that had previously characterized LCM-RNAseq. Our results reveal clear differences abundance between stroma, which by extracellular matrix, cytoskeleton, cytokines such as TNF. The proteomics- RNAseq-based analyses LCM-FFPE show substantial degree correlation, especially for most deregulated targets comparable activation pathways. Finally, validate upregulation LTBP2, IGFBP2, COL6A5, POSTN, FN1, COL4A1, COL12A1, PLOD2, COL4A2, IGFBP7 on level demonstrate their adverse prognostic value breast cancer. Given relevance model disease, our analysis substantiates disease-promoting stromal components implications cancer both species.