Transcriptional Profiling of Breast Cancer Metastases Identifies Liver Metastasis-Selective Genes Associated with Adverse Outcome in Luminal A Primary Breast Cancer
2016 (English)In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 22, no 1, 146-157 p.Article in journal (Refereed) PublishedText
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.
Place, publisher, year, edition, pages
AMER ASSOC CANCER RESEARCH , 2016. Vol. 22, no 1, 146-157 p.
IdentifiersURN: urn:nbn:se:liu:diva-124483DOI: 10.1158/1078-0432.CCR-15-0487ISI: 000367550300018PubMedID: 26276891OAI: oai:DiVA.org:liu-124483DiVA: diva2:899702
Funding Agencies|Swedish Cancer Society; Swedish Research Council; Gunnar Nilsson Cancer Foundation; Berta Kamprad Foundation; Gyllenstierna Krapperups Foundation; Swedish Cancer and Allergy Foundation; Research Funds at Radiumhemmet; Swedish Breast Cancer Association; ALF/FOU research funds at the Karolinska Institutet; Stockholm County Council; Bristol-Myers Squibb Sweden AB; Pfizer Sweden AB; Roche Sweden AB2016-02-022016-02-012016-02-02