Portrait of Molecular Signaling and Putative Therapeutic Targets in Prostate Cancer with ETV4 Fusion

Abstract

Gene fusion between androgen receptor (AR) response genes and E26 transformation-specific (ETS) family members increases the gene expression of ETS family members, and promotes tumorigenesis in prostate cancer. However, the molecular features of ETV4 fusion in prostate cancer are not fully understood, and drugs targeting ETV4 fusion have not been developed. To examine key cellular signaling pathways and explore therapeutic targets and drugs for ETV4-fusion-positive prostate cancer, we analyzed RNA sequencing data and clinical information for prostate cancer. The ETV4-fusion-positive group was selected through prior study and analysis comparing ETV4-fusion-positive and -negative groups was conducted using a Pearson correlation test. We obtained 393 genes correlated with ETV4 expression. Pathway analysis was performed using over-representation analysis (ORA), and six cancer-specific molecular signaling pathways (the irinotecan pathway, metabolism, androgen receptor signaling, interferon signaling, MAPK/NF-kB signaling, and the tamoxifen pathway) were altered in the ETV4-fusion-positive group. Furthermore, a gene–drug database was used to find an actionable drug and therapeutic target for the ETV4-fusion-positive group. Here, we have identified significantly altered genes and oncogenic signaling pathways in ETV4-fusion-positive prostate cancer, and we suggest therapeutic targets and potential drugs for ETV4-fusion-positive prostate patients.