Project description:We aimed to validate an 18-gene classifier (GC) initially developed to predict local/regional recurrence (LRR) after mastectomy in estimating distant metastasis risk.
Project description:We report an upregulation of miR-16 in Paget's disease of bone which is to target the SQSTM1. When miR-16 is lost in Paget's disease, there is malignant transformation.
Project description:We extracted total RNA from fingerstick samples of normal, chondrosarcoma and Paget's disease patients. We then constructed small RNA libraries using HD adapters in order to identify small RNA biomarkers
Project description:Purpose: Several risk factors for local recurrence of breast cancer after breast conserving therapy (BCT) have been identified. The identification of additional risk factors would be very useful in guiding optimal therapy and also improve understanding of the mechanisms underlying local recurrence. We used cDNA microarray analysis to identify gene expression profiles associated with local recurrence. Experimental Design: Using 18K cDNA microarrays, gene expression profiles were obtained from 50 patients who underwent BCT. Of these 50 patients 19 developed a local recurrence; the remaining 31 patients were selected as controls as they were free of local recurrence at least 11 years after treatment. For 9/19 patients also the local recurrence was available for gene expression profiling. Unsupervised and supervised methods of classification were used to separate patients in groups corresponding to disease outcome and to study the overall gene expression pattern of primary tumors and their recurrences. Results: Hierarchical clustering of patients did not show any grouping reflecting local recurrence status. Supervised analysis revealed no significant set of genes that was able to distinguish recurring tumors from non-recurring tumors. Paired-data analysis of primary tumors and local recurrences showed a remarkable similarity in gene expression profile between primary tumors and their recurrences. Conclusions: No significant differences in gene expression between primary breast cancer tumors in patients with or without local recurrence after breast conserving therapy were identified. Furthermore, analyses of primary tumors and local recurrences show a preservation of the overall gene expression pattern in the local recurrence, even after radiotherapy. Keywords: gene expression profiling
Project description:Introduction: Overall survival of early-stage breast cancer (BC) patients is similar for those who undergo breast conserving therapy (BCT) and mastectomy, however, 10-15% of women undergoing BCT suffer ipsilateral breast tumor recurrence. The risk of recurrence may vary with age or breast cancer subtype. Understanding the gene expression of the cancer-adjacent tissue and/or stromal response to specific tumor subtypes is important for developing clinical strategies to reduce recurrence risk. Methods: We studied gene expression data in cancer-adjacent tissue from 158 BC patients. Complementary in vitro cocultures were used to study cell-cell communication between fibroblasts and specific breast cancer subtypes. Results: Our results suggest that intrinsic tumor subtypes are reflected in histologically normal cancer-adjacent tissue. Gene expression of cancer-adjacent tissues shows that triple negative (Claudin-low or Basal-like tumors) exhibit increased expression of genes involved in inflammation and immune response. While such changes could reflect distinct immune populations present in the microenvironment of different breast cancer subtypes, altered immune response gene expression was also observed in cocultures in the absence of immune cell infiltrates, emphasizing that these inflammatory mediators are secreted by breast-specific cells. In addition, while triple negative BCs are associated with upregulated immune response genes, Luminal breast cancers are more commonly associated with estrogen-response in adjacent tissues. Conclusions: Specific characteristics of BCs are reflected in the surrounding benign tissue. This commonality between tumor and surrounding tissue may underlie second primaries and local recurrences. Biomarkers derived from cancer-adjacent tissue may be helpful in defining personalized surgical strategies or in predicting recurrence risk. reference x sample
Project description:Background: While body fluids are widely used in medicine, despite the fact that interstitial fluid (IF) represents a third of our body fluid, it is the most poorly understood and under-studied. In cancer, IF pressure is elevated due to increased extracellular matrix deposition in the desmoplastic stroma surrounding tumors. However, whether IF affects cancer behavior remains unclear. Methods: We collected 180 IF using drains from patients that underwent bilateral mastectomy for unilateral breast cancer with or without immediate reconstruction. The IF were classified based on their ability to promote invasion of breast cancer cells and tested in vivo. A retrospective study linking IF-invasion score to clinical parameters was performed. Results: We observed a wide range of invasion score among IF between patients, and analysis of different IF from the same patient suggests that IF are organ-specific. Patients with high-grade tumors at diagnosis have high score IF. In mice, injections of high-score IF in a normal mammary gland promoted ductal hyperplasia, increased collagen deposition and local invasion. In a mouse model of residual disease, high-score IF increased local recurrence and promoted aggressive visceral metastases. Discussion: Exposure of normal breasts to high-score IF predisposes to the development of aggressive breast cancer long before surgery. Further, such exposure following surgery increases the risk of recurrence. Therefore, our study raises the provocative possibility that intrinsic difference in IF between individuals play an active role in the predisposition, development and clinical course of sporadic breast cancers.