Transcriptional Profiling of Breast Cancer Metastases Identifies Liver Metastasis-Selective Genes Associated with Adverse Outcome in Luminal A Primary Breast Cancer

被引：39

作者：

Kimbung, Siker ^{[1
,2
]}

Johansson, Ida ^{[1
,2
]}

Danielsson, Anna ^{[3
]}

Veerla, Srinivas ^{[1
,2
]}

Brage, Suzanne Egyhazi ^{[4
,5
]}

Stolt, Marianne Frostvik ^{[4
,5
]}

Skoog, Lambert ^{[4
,5
]}

Carlsson, Lena ^{[6
]}

Einbeigi, Zakaria ^{[3
]}

Lidbrink, Elisabet ^{[4
,5
]}

Linderholm, Barbro ^{[3
]}

Loman, Niklas ^{[7
]}

Malmstrom, Per-Olof ^{[7
]}

Soderberg, Martin ^{[7
]}

Walz, Thomas M. ^{[8
]}

Ferno, Marten ^{[1
]}

Hatschek, Thomas ^{[4
,5
]}

Hedenfalk, Ingrid ^{[1
,2
]}

机构：

[1] Lund Univ, Div Oncol & Pathol, Dept Clin Sci, SE-22381 Lund, Sweden

[2] Lund Univ, CREATE Hlth Strateg Ctr Translat Canc Res, SE-22381 Lund, Sweden

[3] Univ Gothenburg, Inst Clin Sci, Sahlgrenska Acad, Dept Oncol, Gothenburg, Sweden

[4] Karolinska Inst, Dept Oncol & Pathol, S-10401 Stockholm, Sweden

[5] Karolinska Univ Hosp, Stockholm, Sweden

[6] Sundsvall Hosp, Dept Oncol, Sundsvall, Sweden

[7] Skane Univ Hosp, Dept Oncol, Lund, Sweden

[8] Linkoping Univ, Fac Hlth Sci, Dept Clin & Expt Med, Div Oncol, Linkoping, Sweden

来源：

CLINICAL CANCER RESEARCH | 2016年 / 22卷 / 01期

基金：

瑞典研究理事会;

关键词：

EXPRESSION PROFILES; BONE METASTASIS; MANAGEMENT; CLAUDIN-2; WOMEN; LUNG; SITE;

D O I：

10.1158/1078-0432.CCR-15-0487

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：146 / 157

页数：12

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