Gene Expression Profiling Of The Breast Tumour Microenvironment
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Gene Expression Profiling Of The Breast Tumour Microenvironment
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Author : Grzegorz Finak
language : en
Publisher:
Release Date : 2008
Gene Expression Profiling Of The Breast Tumour Microenvironment written by Grzegorz Finak and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2008 with categories.
"Breast cancer is a very heterogeneous disease. This heterogeneity can be observed at many levels, including gene expression, chromosomal aberrations, and disease pathology. A clear understanding of these differences is important since they impact upon treatment efficacy and clinical outcome. Recent studies have demonstrated that the tumour microenvironment also plays a critical role in cancer initiation and progression. Genomic technologies have been used to gain a better understanding of the impact of gene expression heterogeneity on breast cancer, and have identified gene expression signatures associated with clinical outcome, histopathological breast cancer subtypes, and a variety of cancer-related pathways and processes. However, little work has been done in this context to examine the role of the tumour microenvironment in determining breast cancer outcome, or in defining breast cancer heterogeneity. Additionally, little is known about gene expression in histologically normal tissue adjacent to breast tumour, if this is influenced by the tumour, and how this compares with non-tumour-bearing breast tissue. By applying laser--capture microdissection and gene expression profiling to clinical breast cancer specimens the research presented in this thesis addresses these questions. We have generated gene expression profiles of morphologically normal epithelial and stromal tissue, isolated using laser capture microdissection, from patients with breast cancer or undergoing breast reduction mammoplasty. We determined that morphologically normal epithelium and stroma exhibited distinct expression profiles, but molecular signatures that distinguished breast reduction tissue from tumour-adjacent normal tissue were absent. Stroma isolated from morphologically normal ducts adjacent to tumour tissue contained two distinct expression profiles that correlated with stromal cellularity, and shared similarities with soft tissue tumors with favourable outcome. Adjacent normal epithelium and stroma from breast cancer patients showed no significant association between expression profiles and standard clinical characteristics, but did cluster ER/PR/HER2-negative breast cancers with basal-like subtype expression profiles with poor prognosis. Our data reveal that morphologically normal tissue adjacent to breast carcinomas has not undergone significant gene expression changes when compared to breast reduction tissue, and provide an important gene expression data set for comparative studies of tumour expression profiles. We compared gene expression profiles of tumour stroma from primary breast tumors and derived signatures strongly associated with clinical outcome. We present a new stroma-derived prognostic predictor (SDPP) that stratifies disease outcome independently of standard clinical prognostic factors and published expression-based predictors. The SDPP predicts outcome in several published whole tumour--derived expression data sets, identifies poor-outcome individuals from multiple clinical subtypes, including lymph node--negative tumors, and shows increased accuracy with respect to previously published predictors, especially for HER2-positive tumors. Prognostic power increases substantially when the predictor is combined with existing outcome predictors. Genes represented in the SDPP reveal the strong prognostic capacity of differential immune responses as well as angiogenic and hypoxic responses, highlighting the importance of stromal biology in tumour progression. We show that gene expression in the breast tumour microenvironment is highly heterogeneous, identifying at least six different classes of tumour stroma with distinct expression patterns and distinct biological processes. Two of these classes recapitulate the processes identified in the stroma-derived prognostic predictor, while the others are new classes of stroma associated with distinct clinical outcomes. One of these is associated with matrix remodelling and is strongly associated with the basal molecular subtype of breast cancer. The remainder are independent of the previously published molecular subtypes of breast cancer. Additionally, based on independent data from over 800 tumors, the combinations of stroma classes and breast cancer subtypes identify new subgroups of breast tumors that show better discrimination between good and poor outcome individuals than the molecular breast cancer subtypes or the stroma classes alone, suggesting a novel classification scheme for breast cancer. This research demonstrates an important role for the tumour microenvironment in defining breast cancer heterogeneity, with a consequent impact upon clinical outcome. Novel therapies could be targeted at the processes that define the stroma classes suggesting new avenues for individualized treatment."--
Gene Expression Profiling Of The Breast Tumour Microenvironment And Its Influence On Clinical Outcome
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Author : Grzegorz Finak
language : en
Publisher:
Release Date : 2008
Gene Expression Profiling Of The Breast Tumour Microenvironment And Its Influence On Clinical Outcome written by Grzegorz Finak and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2008 with categories.
Impact Of Gene Expression Profiling Tests On Breast Cancer Outcomes
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Author : Luigi Marchionni
language : en
Publisher: DIANE Publishing
Release Date : 2009-05
Impact Of Gene Expression Profiling Tests On Breast Cancer Outcomes written by Luigi Marchionni and has been published by DIANE Publishing this book supported file pdf, txt, epub, kindle and other format this book has been release on 2009-05 with Medical categories.
Assesses the evidence that three marketed gene expression-based assays improve prognostic accuracy, treatment choice, and health outcomes in women diagnosed with early stage breast cancer. Three gene expression assays were evaluated; Oncotype DX¿, MammaPrint® and the Breast Cancer Profiling (BCP or H/I ratio) test, and for gene expression signatures underlying the assays. They sought evidence on: analytic performance of tests; clinical validity; clinical utility; harms; and impact on clinical decision making and health care costs. Conclusions: Oncotype DX is furthest along the validation pathway, with retrospective evidence that it predicts distant spread and chemotherapy benefit to a clinically relevant extent over standard predictors. Illus.
Bioinformatics Approaches To Understanding The Breast Cancer Microenvironment
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Author : François Pepin
language : en
Publisher:
Release Date : 2010
Bioinformatics Approaches To Understanding The Breast Cancer Microenvironment written by François Pepin and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2010 with categories.
Defining Microenvironment Induced Transcription Profiles In Breast Cancer Liver Metastases
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Author : Christine Tam
language : en
Publisher:
Release Date : 2014
Defining Microenvironment Induced Transcription Profiles In Breast Cancer Liver Metastases written by Christine Tam and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2014 with categories.
"Breast cancer is the most common type of cancer diagnosed in Canadian women, with metastatic spread contributing to the majority of cancer-related deaths. The liver is the third most frequent site of breast cancer metastasis, but not much is known about the hepatic microenvironment's role in regulating the growth and survival of metastatic cells in the liver. In order to elucidate these interactions, we used laser capture microdissection and microarray analysis to compare gene expression patterns of liver metastases and primary tumors. We employed liver-aggressive 4T1 breast cancer cells derived from an in vivo selection process to generate mammary tumors and liver metastases in female Balb/c mice. Mice with liver metastases were kept for three different time periods post-injection to assess the changes in gene expression during metastatic development. Laser capture microdissection was used to isolate cores and margins of tumors and liver metastases, as well as tumor-adjacent and -distal normal liver. Transcription profiling revealed significant gene expression changes within breast cancer cells growing in the fat pad and the liver microenvironments. We identified a set of immune-related genes overexpressed in the liver metastases that may represent putative myeloid/granulocytic cell markers. Lcn2 and S100a8/S100a9 were found to be exclusively expressed in the immune compartment of liver metastases, particularly within smaller lesions. Since concurrent studies in our laboratory have revealed a similar recruitment of Gr1+/NE+ cells around breast cancer liver metastases, Lcn2 and S100a8/a9 represent interesting avenues with which to investigate the role that these infiltrating cell types play in supporting breast cancer liver metastasis." --
Impact Of Gene Expression Profiling Tests On Breast Cancer Outcomes
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Author : Luigi Marchionni (M.D.)
language : en
Publisher:
Release Date : 2008-01-01
Impact Of Gene Expression Profiling Tests On Breast Cancer Outcomes written by Luigi Marchionni (M.D.) and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2008-01-01 with Breast categories.
Tumor Microenvironment
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Author : Peter P. Lee
language : en
Publisher: Springer Nature
Release Date : 2020-03-25
Tumor Microenvironment written by Peter P. Lee and has been published by Springer Nature this book supported file pdf, txt, epub, kindle and other format this book has been release on 2020-03-25 with Medical categories.
This book addresses the biological processes relevant to the immune phenotypes of cancer and their significance for immune responsiveness, based on the premise that malignant cells manipulate their surroundings through an evolutionary process that is controlled by interactions with innate immune sensors as well as the adaptive recognition of self/non-self. Checkpoint inhibitor therapy is now an accepted new form of cancer treatment. Other immuno-oncology approaches, such as adoptive cell therapy and metabolic inhibitors, have also shown promising results for specific indications. Immune resistance is common, however, limiting the efficacy of immunotherapy in many common cancer types. The reasons for such resistance are diverse and peculiar to the immune landscapes of individual cancers, and to the treatment modality used. Accordingly, approaches to circumvent resistance need to take into account context-specific genetic, biological and environmental factors that may affect the cancer immune cycle, and which can best be understood by studying the target tissue and correlated systemic immune markers. Understanding the major requirements for the evolutionary process governing human cancer growth in the immune-competent host will guide effective therapeutic choices that are tailored to the biology of individual cancers.
The Tumor And Microenvironment Crosstalk In Breast Cancer From Biology To Therapeutic Opportunity
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Author : Marta Truffi
language : en
Publisher: Frontiers Media SA
Release Date : 2024-01-19
The Tumor And Microenvironment Crosstalk In Breast Cancer From Biology To Therapeutic Opportunity written by Marta Truffi and has been published by Frontiers Media SA this book supported file pdf, txt, epub, kindle and other format this book has been release on 2024-01-19 with Medical categories.
A Comparison Of Gene Expression Profiling Tests For Breast Cancer
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Author : Pam Smartt
language : en
Publisher:
Release Date : 2010
A Comparison Of Gene Expression Profiling Tests For Breast Cancer written by Pam Smartt and has been published by this book supported file pdf, txt, epub, kindle and other format this book has been release on 2010 with Breast categories.
The Application Of Gene Expression Profiling To Clinical Breast Cancer Research
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Author : Sherene Loi
language : en
Publisher: LAP Lambert Academic Publishing
Release Date : 2009
The Application Of Gene Expression Profiling To Clinical Breast Cancer Research written by Sherene Loi and has been published by LAP Lambert Academic Publishing this book supported file pdf, txt, epub, kindle and other format this book has been release on 2009 with categories.
The book has three main results parts. Chapter 3 illustrates the first independent validation study of a 70-gene signature developed from gene expression profiling for use in breast cancer prognosis and demonstration of its ability to add independent prognostic information to the clinical prognostic factors currently used. The successful validation of this study preceded the design and implementation of a world-wide randomized clinical trial evaluating the gene signature's clinical utility. This trial has commenced and is currently recruiting in Europe. Chapter 4 describes the finding that proliferation-related genes can predict clinical outcome consistently in breast cancer and many gene signatures developed for predicting breast cancer prognosis derive a significant proportion of their prognostic power from these genes. Finally, chapter 5 describes the use of proliferation-related genes to define two distinct prognostic molecular subgroups within estrogen receptor positive breast cancers.