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Transcriptional Pro...
Transcriptional Profiling of Breast Cancer Metastases Identifies Liver Metastasis-Selective Genes Associated with Adverse Outcome in Luminal A Primary Breast Cancer
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- Kimbung, Siker (author)
- Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund University, Sweden
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- Johansson, Ida (author)
- Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund University, Sweden
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- Danielsson, Anna, 1973 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för onkologi,Institute of Clinical Sciences, Department of Oncology
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- Veerla, Srinivas (author)
- Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund University, Sweden
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- Egyhazi Brage, Suzanne (author)
- Karolinska Institutet
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- Frostvik Stolt, Marianne (author)
- Karolinska Institute, Sweden; Karolinska University Hospital, Sweden
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- Skoog, Lambert (author)
- Karolinska Institutet
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- Carlsson, Lena (author)
- Sundsvall Hospital, Sweden
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- Einbeigi, Zakaria, 1962 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för onkologi,Institute of Clinical Sciences, Department of Oncology
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- Lidbrink, Elisabet (author)
- Karolinska Institute, Sweden; Karolinska University Hospital, Sweden
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- Linderholm, Barbro, 1959 (author)
- Gothenburg University,Göteborgs universitet,Karolinska Institutet,Institutionen för kliniska vetenskaper, Avdelningen för onkologi,Institute of Clinical Sciences, Department of Oncology
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- Loman, Niklas (author)
- Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital, Sweden
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- Malmström, Per (author)
- Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Skåne University Hospital, Sweden
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- Soderberg, Martin (author)
- Skåne University Hospital, Sweden
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- Walz, Thomas (author)
- Linköpings universitet,Avdelningen för kliniska vetenskaper,Hälsouniversitetet,Region Östergötland, Onkologiska kliniken US
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- Ferno, Marten (author)
- Lund University, Sweden
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- Hatschek, Thomas (author)
- Karolinska Institutet
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- Hedenfalk, Ingrid (author)
- Lund University,Lunds universitet,Bröstcancer-genetik,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Breastcancer-genetics,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund University, Sweden; Lund University, Sweden
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(creator_code:org_t)
- AMER ASSOC CANCER RESEARCH, 2016
- 2016
- English.
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In: Clinical Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 1078-0432 .- 1557-3265. ; 22:1, s. 146-157
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Abstract
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- Purpose: The complete molecular basis of the organ-specificity of metastasis is elusive. This study aimed to provide an independent characterization of the transcriptional landscape of breast cancer metastases with the specific objective to identify liver metastasis-selective genes of prognostic importance following primary tumor diagnosis. Experimental Design: A cohort of 304 women with advanced breast cancer was studied. Associations between the site of recurrence and clinicopathologic features were investigated. Fine-needle aspirates of metastases (n = 91) were subjected to whole-genome transcriptional profiling. Liver metastasis-selective genes were identified by significance analysis of microarray (SAM) analyses and independently validated in external datasets. Finally, the prognostic relevance of the liver metastasis-selective genes in primary breast cancer was tested. Results: Liver relapse was associated with estrogen receptor (ER) expression (P = 0.002), luminal B subtype (P = 0.01), and was prognostic for an inferior postrelapse survival (P = 0.01). The major variation in the transcriptional landscape of metastases was also associated with ER expression and molecular subtype. However, liver metastases displayed unique transcriptional fingerprints, characterized by down-regulation of extracellular matrix (i.e., stromal) genes. Importantly, we identified a 17-gene liver metastasis-selective signature, which was significantly and independently prognostic for shorter relapse-free (P < 0.001) and overall (P = 0.001) survival in ER-positive tumors. Remarkably, this signature remained independently prognostic for shorter relapse-free survival (P = 0.001) among luminal A tumors. Conclusions: Extracellular matrix (stromal) genes can be used to partition breast cancer by site of relapse and may be used to further refine prognostication in ER positive primary breast cancer. (C)2015 AACR.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
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- ref (subject category)
- art (subject category)
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- By the author/editor
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Kimbung, Siker
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Johansson, Ida
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Danielsson, Anna ...
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Veerla, Srinivas
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Egyhazi Brage, S ...
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Frostvik Stolt, ...
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show more...
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Skoog, Lambert
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Carlsson, Lena
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Einbeigi, Zakari ...
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Lidbrink, Elisab ...
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Linderholm, Barb ...
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Loman, Niklas
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Malmström, Per
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Soderberg, Marti ...
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Walz, Thomas
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Ferno, Marten
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Hatschek, Thomas
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Hedenfalk, Ingri ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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Clinical Cancer ...
- By the university
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Linköping University
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Lund University
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Karolinska Institutet
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University of Gothenburg