NRC Montreal, 6100 Royalmount Avenue, Canada
- 1. NRC Montreal, 6100 Royalmount Avenue, Canada
- 2. NRC Ottawa, 100 Sussex Drive, Canada
- 3. Formation Biologics, 6100 Royalmount Avenue, Canada
Absract
Targeting of the tumor vasculature has evolved into an integral part of existing standard anti-cancer therapies. However, recent pre-clinical and clinical studies have shown that the efficacy of these treatments is often temporary and frequently followed by renewed tumor growth. In an attempt to overcome this problem we transcriptionally profiled laser capture micro dissected micro vessels from both tumor and matching adjacent normal breast tissue obtained from patients diagnosed with infiltrating ductal carcinoma (IDC). Vascular enrichment of the LCM samples was confirmed by Q-PCR of CD31 and transcription profiles were generated and analyzed using the Genespring software and the WebGestalt Toolkit. Hierarchical two-dimensional clustering of the transcriptome data identified 219 significantly up-regulated transcripts in at least 4/8 patient samples (cut-off >1.3-fold, p<0.05). Several of these genes (i.e. AGRN, FLNA and ILR4) were selected and their over expression was confirmed at the protein level in tumor versus normal tissue. However, the overall heterogeneity we observed in the vascular gene expression patterns pose a significant problem for individual genes/ proteins to be used as a robust breast cancer vascular specific marker or validated therapeutic target. We therefore mined our data set further by applying an in-house developed bioinformatics network method incorporating clinical information of the patient. This approach generated a 15-gene ‘Vascular-Derived Prognostic Predictor’
which, using six publicly available datasets, robustly identified those patients with an increased risk of recurrence.