Site-Specific and Common Prostate Cancer Metastasis Genes as Suggested by Meta-Analysis of Gene Expression Data

Abstract

Anticancer therapies mainly target primary tumor growth and little attention is given to the events driving metastasis formation. Metastatic prostate cancer, in comparison to localized disease, has a much worse prognosis. In the work presented here, groups of genes that are common to prostate cancer metastatic cells from bones, lymph nodes, and liver and those that are site-specific were delineated. The purpose of the study was to dissect potential markers and targets of anticancer therapies considering the common characteristics and differences in transcriptional programs of metastatic cells from different secondary sites. To that end, a meta-analysis of gene expression data of prostate cancer datasets from the GEO database was conducted. Genes with differential expression in all metastatic sites analyzed belong to the class of filaments, focal adhesion, and androgen receptor signaling. Bone metastases undergo the largest transcriptional changes that are highly enriched for the term of the chemokine signaling pathway, while lymph node metastasis show perturbation in signaling cascades. Liver metastases change the expression of genes in a way that is reminiscent of processes that take place in the target organ. Survival analysis for the common hub genes revealed involvements in prostate cancer prognosis and suggested potential biomarkers.