Journal Article

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

Larsson, Christer, Edsjö, Anders, Winslow, Sofia, Lindquist, Kajsa Ericson

2016

Overview

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.

• Publisher: BioMed Central,Springer Nature B.V
• Subject: angiogenesis / Biomedical and Life Sciences / Biomedicine / Breast cancer / Breast Neoplasms - genetics / Breast Neoplasms - mortality / Breast Neoplasms - pathology / Cancer and Oncology / Cancer och onkologi / Cancer Research / cells / Clinical Medicine / Datasets as Topic / ECM metagenes / Endothelial metagenes / Endothelium - metabolism / Endothelium - pathology / Extracellular Matrix - genetics / Extracellular Matrix - metabolism / extracellular-matrix / Female / fibroblasts / Gene expression / Gene Expression Profiling / Gene Expression Regulation, Neoplastic / gene signatures / Genetics / genomics and epigenetics / Health Promotion and Disease Prevention / Humans / Klinisk medicin / Lasers / Medical and Health Sciences / Medical prognosis / Medicin och hälsovetenskap / Medicine/Public Health / metastasis / Oncology / P4HA3 / Polyethylene terephthalate / Prognosis / Proportional Hazards Models / Research Article / Stromal Cells - metabolism / Surgical Oncology / TCF4 / Transcriptome / Tumor stroma / Tumors