CXCR4/CXCL12 Signaling and Protumor Macrophages in Primary Tumors and Sentinel Lymph Nodes Are Involved in Luminal B Breast Cancer Progression.
Carlotta RaschioniGiulia BottaiAndrea SagonaValentina ErricoAlberto TestoriWolfgang GatzemeierFabio CorsiCorrado TinterriMassimo RoncalliLibero SantarpiaLuca Di TommasoPublished in: Disease markers (2018)
Luminal B breast cancers (BC) have a more aggressive behavior associated with a higher rate of tumor relapse and worse prognosis compared to luminal A tumors. In this study, we evaluated the involvement of specific epithelial-to-mesenchymal transition- (EMT-) and immune-related pathways in the dissemination of luminal B BC cells. The expression of 42 EMT- and immune-related genes was evaluated in matched sentinel lymph nodes (SLNs) analyzed by the one-step nucleic acid amplification assay (OSNA) and primary tumors of 40 luminal B BC patients by gene array and immunohistochemistry. The results were validated in an independent group of 150 luminal B tumors by immunohistochemistry and immunofluorescence and using gene expression data from 315 luminal B BC patients included in the Metabric dataset. We found that the expression of CXCR4 (p = 3.28E - 02) and CD163 (p = 6.92E - 03) was significantly upregulated in SLNs of recurrent luminal B BC patients. Luminal B primary tumors overexpressing CXCR4 were characterized by an increased expression of vimentin and a high content of CD163-positive macrophages. Bioinformatics analysis confirmed the correlation of CXCR4 with CXCL12, VIM, and CD163 expression and LN involvement. Our results suggest that the upregulation of the CXCR4/CXCL12 pathway and the presence of protumor macrophages in the primary tumor and SLNs sustain the aggressiveness of an important subgroup of luminal B BC.
Keyphrases
- poor prognosis
- end stage renal disease
- gene expression
- lymph node
- ejection fraction
- newly diagnosed
- chronic kidney disease
- nucleic acid
- prognostic factors
- dna methylation
- peritoneal dialysis
- high throughput
- clinical trial
- patient reported outcomes
- young adults
- genome wide
- machine learning
- epithelial mesenchymal transition
- cell proliferation
- deep learning
- neoadjuvant chemotherapy
- big data
- mass spectrometry
- early stage
- sentinel lymph node