Candidate biomarkers and gene modules investigation for bone tumor samples derived from castration-resistant prostate cancer bone metastasis patients using WGCNA

Abstract

Background About 80-90% of castration-resistant prostate cancer (CRPC) patients would develop bone metastasis, which leads to the disorder of bone metabolism and induces skeletal related events. However, except for the few approved radiotherapeutic and chemotherapy drugs, like radium-223 and denosumab, there is still lack of effective treatment targeting the bone metastatic tumor. It is necessary and significant to explore the mechanisms of bone metastasis and tumorigenesis, especially the differences between the tumor and normal cells in bone after metastatic colonization, which will provide a set of candidate genes for the screening of novel bone targeting agents.Results 4 datasets (GSE32269, GSE101607, GSE29650 and GSE74685) were obtained from the GEO database. 1983 differentially expressed genes (DEGs) were first identified between bone marrow tumor samples and normal marrow samples in GSE32269, followed by the weighted gene co-expression analysis. Most of the top 10 DEGs are found to be related with prostate cancer. 7 co-expression modules were then detected based on the 1469 DEGs shared by the 4 datasets, and 3 of them were found highly preserved among the other three datasets. The top 30 hub genes of the 3 modules were extracted. Among the enriched pathways of preserved modules, Cell adhesion molecules (CAMs) and Leukocyte transendothelial migration might play significant important roles in the tumor development in bone marrow. Literature searches further showed that a set of DEGs and hub genes might also contribute to the development of tumor in bone.Conclusions Together, our findings not only provide outline of expression profile in CRPC bone metastasis, but also screen a set of genes associated with CPRC tumor cell colonization and development of bone tumor, which could be helpful for novel bone targeting agents screening.