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The expression pattern of matrix-producing tumor stroma is of prognostic importance in breast cancer

Winslow, Sofia LU ; Lindquist, Kajsa Ericson LU ; Edsjö, Anders LU and Larsson, Christer LU (2016) In BMC Cancer 16(1).
Abstract

Background: There are several indications that the composition of the tumor stroma can contribute to the malignancy of a tumor. Here we utilized expression data sets to identify metagenes that may serve as surrogate marker for the extent of matrix production and vascularization of a tumor and to characterize prognostic molecular components of the stroma. Methods: TCGA data sets from six cancer forms, two breast cancer microarray sets and one mRNA data set of xenografted tumors were downloaded. Using the mean correlation as distance measure compact clusters with genes representing extracellular matrix production (ECM metagene) and vascularization (endothelial metagene) were defined. Explorative Cox modeling was used to identify... (More)

Background: There are several indications that the composition of the tumor stroma can contribute to the malignancy of a tumor. Here we utilized expression data sets to identify metagenes that may serve as surrogate marker for the extent of matrix production and vascularization of a tumor and to characterize prognostic molecular components of the stroma. Methods: TCGA data sets from six cancer forms, two breast cancer microarray sets and one mRNA data set of xenografted tumors were downloaded. Using the mean correlation as distance measure compact clusters with genes representing extracellular matrix production (ECM metagene) and vascularization (endothelial metagene) were defined. Explorative Cox modeling was used to identify prognostic stromal gene sets. Results: Clustering of stromal genes in six cancer data sets resulted in metagenes, each containing three genes, representing matrix production and vascularization. The ECM metagene was associated with poor prognosis in renal clear cell carcinoma and in lung adenocarcinoma but not in other cancers investigated. Explorative Cox modeling using gene pairs identified gene sets that in multivariate models were prognostic in breast cancer. This was validated in two microarray sets. Two notable genes are TCF4 and P4HA3 which were included in the sets associated with positive and negative prognosis, respectively. Data from laser-microdissected tumors, a xenografted tumor data set and from correlation analyses demonstrate the stroma specificity of the genes. Conclusions: It is possible to construct ECM and endothelial metagenes common for several cancer forms. The molecular composition of matrix-producing cells, rather than the extent of matrix production seem to be important for breast cancer prognosis.

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author
organization
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type
Contribution to journal
publication status
published
subject
keywords
Breast cancer, ECM metagenes, Endothelial metagenes, P4HA3, TCF4, Tumor stroma
in
BMC Cancer
volume
16
issue
1
publisher
BioMed Central
external identifiers
  • scopus:84994320635
  • wos:000387642800001
ISSN
1471-2407
DOI
10.1186/s12885-016-2864-2
language
English
LU publication?
yes
id
b83700c1-2c19-40a6-8f67-49b514e30535
date added to LUP
2016-12-01 12:08:46
date last changed
2017-06-25 04:56:35
@article{b83700c1-2c19-40a6-8f67-49b514e30535,
  abstract     = {<p>Background: There are several indications that the composition of the tumor stroma can contribute to the malignancy of a tumor. Here we utilized expression data sets to identify metagenes that may serve as surrogate marker for the extent of matrix production and vascularization of a tumor and to characterize prognostic molecular components of the stroma. Methods: TCGA data sets from six cancer forms, two breast cancer microarray sets and one mRNA data set of xenografted tumors were downloaded. Using the mean correlation as distance measure compact clusters with genes representing extracellular matrix production (ECM metagene) and vascularization (endothelial metagene) were defined. Explorative Cox modeling was used to identify prognostic stromal gene sets. Results: Clustering of stromal genes in six cancer data sets resulted in metagenes, each containing three genes, representing matrix production and vascularization. The ECM metagene was associated with poor prognosis in renal clear cell carcinoma and in lung adenocarcinoma but not in other cancers investigated. Explorative Cox modeling using gene pairs identified gene sets that in multivariate models were prognostic in breast cancer. This was validated in two microarray sets. Two notable genes are TCF4 and P4HA3 which were included in the sets associated with positive and negative prognosis, respectively. Data from laser-microdissected tumors, a xenografted tumor data set and from correlation analyses demonstrate the stroma specificity of the genes. Conclusions: It is possible to construct ECM and endothelial metagenes common for several cancer forms. The molecular composition of matrix-producing cells, rather than the extent of matrix production seem to be important for breast cancer prognosis.</p>},
  articleno    = {841},
  author       = {Winslow, Sofia and Lindquist, Kajsa Ericson and Edsjö, Anders and Larsson, Christer},
  issn         = {1471-2407},
  keyword      = {Breast cancer,ECM metagenes,Endothelial metagenes,P4HA3,TCF4,Tumor stroma},
  language     = {eng},
  month        = {11},
  number       = {1},
  publisher    = {BioMed Central},
  series       = {BMC Cancer},
  title        = {The expression pattern of matrix-producing tumor stroma is of prognostic importance in breast cancer},
  url          = {http://dx.doi.org/10.1186/s12885-016-2864-2},
  volume       = {16},
  year         = {2016},
}