Project description:Genome wide DNA methylation profiling of tumor adjacent normal tissue from patients with invasive breast cancer, as well as tissue from women undergoing reduction mammoplasty or prophylactic surgery. The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 485,577 CpGs in snap frozen breast tissue. Samples included 70 tumor-adjacent normal breast tissue with invasive disease, 8 tissues from breast prophylactic patients, and 18 tissues from breast reduction patients.
Project description:Genome wide DNA methylation profiling of tumor adjacent normal tissue from patients with invasive breast cancer, as well as tissue from women undergoing reduction mammoplasty or prophylactic surgery. The Illumina Infinium 450k Human DNA methylation Beadchip was used to obtain DNA methylation profiles across approximately 485,577 CpGs in snap frozen breast tissue. Samples included 70 tumor-adjacent normal breast tissue with invasive disease, 8 tissues from breast prophylactic patients, and 18 tissues from breast reduction patients. Bisulphite converted DNA from the 96 samples were hybridized to the Illumina Infinium 450k Human Methylation Beadchip.
Project description:To discriminate miRNA expression differences between adjacent normal and tumor tissues of breast cancer. 101 breast tumor + 15 adjacent breast normal tissue samples.
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:The purpose of this study was to understand the genomic and metabolomic changes in the breast tissue microenvironment at various stages of cancer development and progression (i.e. normal breast, DCIS, benign disease and invasive cancer). To understand the way in which metabolic microenvironments evolve with breast cancer, this study analyzed normal breast tissue adjacent to benign and malignant lesions at various stages of cancer development and studied samples adjacent to invasive cancers of distinct breast cancer subtypes.
Project description:MS spectrum of lung tissue metabolic analysis in 131 patients with lung cancer or benign lung tumor. These include lung cancer tissues/benign tumor tissues, adjacent normal tissues and distal normal tissues.
Project description:Aggressive breast tumors are routinely treated with pre-operative chemotherapy. However, a subset of patients have recurrence despite adjuvant treatment. To identify metabolic processes involved in drug resistance, we took a mass spectrometry-based proteomic approach, and analyzed a breast cancer cohort of 113 samples comprising of breast tumors before and after chemotherapy, with matched tumor adjacent normal tissue from partial responders that underwent neoadjuvant treatment (NAT). Pattern analysis of 7180 proteins revealed more than 1000 proteins with significantly differential expression in primary tumor relative to the healthy tissue, which do not respond to treatment, in treatment resistant patients. Among those, we found significant upregulation of the proline biosynthesis pathway, primarily, PYCR1 that significantly correlated with lower recurrence free survival time in our cohort. Functional analysis showed that PYCR1 induced a pro-survival effect upon treatment with chemotherapy drugs thus emphasizing the potential role of PYCR1 in drug resistance in advanced breast cancer.
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.