Transient Receptor Potential Channels in Prostate Cancer: Associations with ERG Fusions and Survival

Calcium movement and concentration in the cell plays significant roles in normal physiology and in diseases such as cancer. The significance of this ion in oncogenesis suggests that membrane-relevant proteins are involved in its regulation and are deregulated in various cancers. These channels and transporters could be targets for therapeutic interventions. An evaluation of the expression of transient receptor potential (TRP) channels in prostate cancer was performed using publicly available genomic and proteome data. Two TRP family members with high expression in prostate cancers, TRPML2 and TRPM4, were chosen for further analysis the uncover the associations of their level of expression with clinical and pathologic prostate cancer characteristics. Several TRP channels were expressed in prostate cancers at the protein level including TRPM4, TRPML1, TRPML2, TRPC1 and TRPP3. At the mRNA level, MCOLN2 and TRPM4 were strongly expressed in a sub-set of prostate cancers. Cases with high MCOLN2 mRNA expression were associated with frequent ERG fusions and a trend for better survival outcomes. In contrast, prostate cancer cases with high TRPM4 mRNA expression were associated with lower ERG fusion frequency than cases with low TRPM4 mRNA expression. The prognosis of prostate cancers with high TRPM4 expression was not different from the prognosis with counterparts having low TRPM4 mRNA expression. TRP channels were expressed in sub-sets of prostate cancers. The two well-expressed channels of the super family, TRPML2 and TRPM4, have divergent associations with the most prevalent prostate cancer molecular aberrations, ERG fusions. These results imply diverse regulations of the TRP channels that would have to be taken into consideration when devising therapeutic interventions targeting individual channels.