Title |
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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Published in |
Clinical Cancer Research, January 2016
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DOI | 10.1158/1078-0432.ccr-15-0487 |
Pubmed ID | |
Authors |
Siker Kimbung, in collaboration with the TEX study group, Ida Johansson, Anna Danielsson, Srinivas Veerla, Suzanne Egyhazi Brage, Marianne Frostvik Stolt, Lambert Skoog, Lena Carlsson, Zakaria Einbeigi, Elisabet Lidbrink, Barbro Linderholm, Niklas Loman, Per-Olof Malmström, Martin Söderberg, Thomas M. Walz, Mårten Fernö, Thomas Hatschek, Ingrid Hedenfalk |
Abstract |
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. A cohort of 304 women with advanced breast cancer was studied. Associations between the site of recurrence and clinico-pathological 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. Liver relapse was associated with estrogen receptor (ER) expression (P=0.002), luminal B subtype (P=0.01), and was prognostic for an inferior post-relapse 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. 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. |
X Demographics
Geographical breakdown
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United States | 1 | 25% |
Unknown | 3 | 75% |
Demographic breakdown
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Members of the public | 4 | 100% |
Mendeley readers
Geographical breakdown
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Denmark | 1 | 1% |
Germany | 1 | 1% |
Norway | 1 | 1% |
Unknown | 63 | 94% |
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Researcher | 17 | 25% |
Student > Bachelor | 10 | 15% |
Student > Ph. D. Student | 7 | 10% |
Student > Master | 7 | 10% |
Lecturer | 3 | 4% |
Other | 10 | 15% |
Unknown | 13 | 19% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 14 | 21% |
Agricultural and Biological Sciences | 11 | 16% |
Nursing and Health Professions | 2 | 3% |
Psychology | 2 | 3% |
Other | 3 | 4% |
Unknown | 19 | 28% |