Gene expression signature of castrate resistant prostate cancer.

ABSTRACT

Prostate gland is a highly androgen dependent gland and hence the first line of treatment for metastatic prostate cancer happens to be androgen ablation. This is achieved by multiple non-surgical methods. However, most of these cancers although respond well initially, become resistant to androgen ablation sooner or later. These cancers then become extremely aggressive and difficult to treat, thereby drastically affect the patient prognosis. Identification of a gene expression signature for castrate resistant prostate cancer may aid in identification of mechanisms responsible for castrate resistance, which in turn would help in better management of the disease. METHODS: Patient samples belonging to a. Control group; b. Castrate Sensitive group and c. Castrate Resistant group were collected. Gene expression profiling was performed on these samples using RNA-seq. Differentially expressed genes between control and castrate sensitive as well as control and castrate resistant groups were identified. This data was compared with data from The Cancer Genome Atlas (TCGA) in order to get relevance in prognosis. RESULTS: We have identified 481 differentially expressed genes between control and castrate sensitive groups; and 446 genes differentially expressed between control and castrate resistant groups. We have also identified 364 genes which are expressed in the castrate resistant group alone, which is of interest since these may have an implication in evolution of castrate resistance and also prognosis. When compared to prostate cancer data from TCGA, 763 genes were found in common to our dataset. With this, a CaS and CaR signature was defined. Using criteria such as overall survival, disease-free survival, progression-free survival and biochemical recurrence, we have identified genes that may have relevance in progression to castrate resistance and in prognosis. Functional annotation of these genes may give an insight into the mechanism of development of castrate resistance.