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Expression of the chemokine CXCL14 in the tumour stroma is an independent marker of survival in breast cancer

Sjöberg, Elin; Augsten, Martin; Bergh, Jonas; Jirström, Karin LU and Östman, Arne (2016) In British Journal of Cancer 114(10). p.1117-1124
Abstract

Background:Expression of the chemokine CXCL14 has previously been shown to be elevated in the tumour stroma of, for example, prostate and breast cancer. Cancer-associated fibroblast-derived CXCL14 enhances tumour growth in mouse models of prostate and breast cancer. However, the prognostic significance of compartment-specific expression of CXCL14 has not been studied.Methods:CXCL14 mRNA expression was analysed in a breast cancer tissue microarray (TMA) of formalin-fixed, paraffin-embedded tumours by the RNAscope 2.0 Assay. Epithelial and stromal expression was analysed separately and correlated with clinicopathological characteristics and survival.Results:CXCL14 was variably and independently expressed in malignant and stromal cells of... (More)

Background:Expression of the chemokine CXCL14 has previously been shown to be elevated in the tumour stroma of, for example, prostate and breast cancer. Cancer-associated fibroblast-derived CXCL14 enhances tumour growth in mouse models of prostate and breast cancer. However, the prognostic significance of compartment-specific expression of CXCL14 has not been studied.Methods:CXCL14 mRNA expression was analysed in a breast cancer tissue microarray (TMA) of formalin-fixed, paraffin-embedded tumours by the RNAscope 2.0 Assay. Epithelial and stromal expression was analysed separately and correlated with clinicopathological characteristics and survival.Results:CXCL14 was variably and independently expressed in malignant and stromal cells of breast cancer. Total and stromal expression of CXCL14 did not associate with clinicopathological parameters. Epithelial CXCL14 expression was significantly associated with oestrogen receptor α (ERα)-positive tumours and lower proliferation status. Total CXCL14 expression correlated significantly with shorter breast cancer-specific and recurrence-free survival. High stromal, but not epithelial, CXCL14 expression was significantly associated with shorter survival in univariable and multivariable analyses. Moreover, the correlation between stromal CXCL14 expression and survival was more prominent in ER negative, triple negative and basal-like breast cancers.Conclusions:The identification of prognostic significance of stromal CXCL14 in breast cancer demonstrates novel clinical relevance of a stroma-derived secreted factor and illustrates the importance of tumour compartment-specific analyses. On the basis of the prognostic signals from difficult-to-treat subgroups, CXCL14 should also be considered as a candidate drug target.

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organization
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Contribution to journal
publication status
published
subject
keywords
breast cancer, chemokines, CXCL14, prognosis, tumour microenvironment, tumour stroma, tumour stroma secretome
in
British Journal of Cancer
volume
114
issue
10
pages
8 pages
publisher
Nature Publishing Group
external identifiers
  • scopus:84966546726
  • wos:000376430800015
ISSN
0007-0920
DOI
10.1038/bjc.2016.104
language
English
LU publication?
yes
id
291c44bb-79a1-4512-be7c-bf79c9f9162b
date added to LUP
2016-06-02 16:14:37
date last changed
2017-04-23 04:51:03
@article{291c44bb-79a1-4512-be7c-bf79c9f9162b,
  abstract     = {<p>Background:Expression of the chemokine CXCL14 has previously been shown to be elevated in the tumour stroma of, for example, prostate and breast cancer. Cancer-associated fibroblast-derived CXCL14 enhances tumour growth in mouse models of prostate and breast cancer. However, the prognostic significance of compartment-specific expression of CXCL14 has not been studied.Methods:CXCL14 mRNA expression was analysed in a breast cancer tissue microarray (TMA) of formalin-fixed, paraffin-embedded tumours by the RNAscope 2.0 Assay. Epithelial and stromal expression was analysed separately and correlated with clinicopathological characteristics and survival.Results:CXCL14 was variably and independently expressed in malignant and stromal cells of breast cancer. Total and stromal expression of CXCL14 did not associate with clinicopathological parameters. Epithelial CXCL14 expression was significantly associated with oestrogen receptor α (ERα)-positive tumours and lower proliferation status. Total CXCL14 expression correlated significantly with shorter breast cancer-specific and recurrence-free survival. High stromal, but not epithelial, CXCL14 expression was significantly associated with shorter survival in univariable and multivariable analyses. Moreover, the correlation between stromal CXCL14 expression and survival was more prominent in ER negative, triple negative and basal-like breast cancers.Conclusions:The identification of prognostic significance of stromal CXCL14 in breast cancer demonstrates novel clinical relevance of a stroma-derived secreted factor and illustrates the importance of tumour compartment-specific analyses. On the basis of the prognostic signals from difficult-to-treat subgroups, CXCL14 should also be considered as a candidate drug target.</p>},
  author       = {Sjöberg, Elin and Augsten, Martin and Bergh, Jonas and Jirström, Karin and Östman, Arne},
  issn         = {0007-0920},
  keyword      = {breast cancer,chemokines,CXCL14,prognosis,tumour microenvironment,tumour stroma,tumour stroma secretome},
  language     = {eng},
  month        = {05},
  number       = {10},
  pages        = {1117--1124},
  publisher    = {Nature Publishing Group},
  series       = {British Journal of Cancer},
  title        = {Expression of the chemokine CXCL14 in the tumour stroma is an independent marker of survival in breast cancer},
  url          = {http://dx.doi.org/10.1038/bjc.2016.104},
  volume       = {114},
  year         = {2016},
}