Unknown,Transcriptomics,Genomics,Proteomics

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Mesenchymal cancer cell-stromal crosstalk promotes niche activation, epithelial reversion and metastatic colonization

ABSTRACT: The experiment was design to address the intrinsic differences between metastatic cancer stem cells in the primary tumour and during metastatic colonization in the mouse mammary gland tumour model MMTV-pyMT. Total RNA was prepared from the indicated cancer cells freshly isolated, stained and FACS sorted either from primary tumours or from lungs upon intravenous injection of cancer cells.

ORGANISM(S): Mus musculus

SUBMITTER: Ilaria Malanchi

PROVIDER: E-GEOD-63558 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Background: Gene expression profiling has been used extensively within breast cancer research. Patient matched transcriptomic studies of tumour samples before and after treatment offer great potential and have been initiated, but tend not to include a control group. Here we examine gene expression changes between patient-matched core biopsies and surgical resection samples in the absence of treatment, to consider sampling methods and tumour heterogeneity. Patients and Methods: Illumina BeadArray technology was used to measure dynamic changes in gene expression from thirty-seven paired baseline and surgically excised breast tumour samples obtained from women receiving no treatment prior to surgery. Results: Patient-matched sample pairs had significantly higher correlations than samples between different individuals, demonstrating that tumour heterogeneity and intra-tumour differences are less prominent than inter-tumour/patient differences. Perhaps surprisingly, consistent changes in gene expression were identified during the diagnosis-surgery interval, despite a lack of treatment. 50 genes were significantly differentially expressed (48 up, 2 down; FDR 0.05) in a manner that appears independent of both subtype and the sampling-interval length. Gene set enrichment analysis using four independent treated datasets has implicated the tumour sampling method as the likely cause of these expression changes which include increases in early growth response genes such as EGR1, 2 and 3 along with DUSP1 and FOS. Our data does not support the idea that there is a significant wounding or immune response. Conclusion: This is the largest cohort of patient-matched transcriptome profiling of tumours from patients receiving no treatment between diagnosis and surgery to date. It has revealed that consistent changes in gene expression do exist between diagnostic core biopsy and the surgical excision sample. We have confirmed these findings in a number of published breast cancer datasets. Ultimately, researchers should be aware of the potential for the tumour sampling method to introduce a confounding factor in future neoadjuvant studies. 37 paired patient-matched whole-transcriptome profiled primary breast tumours from patients receiving no treatment between diagnosis and surgery. Superseries is a product of two integrated individual batches.

Dataset Information

Mesenchymal cancer cell-stromal crosstalk promotes niche activation, epithelial reversion and metastatic colonization

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