Genetic alterations of interleukin-17 and related genes in human prostate cancer.

Interleukin-17 (IL-17) has been shown to promote development of hormone-naïve prostate cancer (HNPC) and castration-resistant prostate cancer (CRPC) as well as lymph node metastasis in mouse models. Gene alterations of IL-17 family of cytokines and their downstream genes in human prostate cancer have not been investigated. We studied 7 datasets archived in cBioPortal and queried gene alterations in a total of 1303 cases of human prostate cancers. 35 genes were examined, including IL-17 family of cytokines and receptors, IL-17-downstream genes, and genes related to IL-17-downstream genes. We found that 34/35 (97%) genes had significantly more alterations in metastatic prostate cancer (with alteration rates ranging from 3.42% to 13.01%) than primary prostate cancer (with alteration rates ranging from 0.40% to 2.96%). 15/35 (43%) genes had significantly more alterations in primary CRPC than primary HNPC. 34/35 (97%) genes had significantly more alterations in metastatic CRPC than primary HNPC. Only three genes (S100A7, S100A8, and S100A9) had significantly more alterations in metastatic CRPC than primary CRPC. The gene alterations were mostly gene amplifications (97%), while gene deep deletions, missense mutations, and truncating mutations were very rare. 7/35 (20%) genes had significantly more alterations in primary neuroendocrine prostate cancer (NEPC) than primary adenocarcinoma (AC). 23/35 (66%) genes had significantly more alterations in metastatic NEPC than metastatic AC. Only three genes (S100A7, S100A8, and S100A9) had significantly more alterations in metastatic NEPC than metastatic AC with neuroendocrine features. Most of the gene alterations in metastatic NEPC were gene amplifications (80%), while gene deep deletions, missense mutations, and truncating mutations were very rare. Our findings suggest that gene amplifications of IL-17 and related genes are more frequently found in metastatic CRPC and NEPC than primary hormone-naïve prostate adenocarcinomas, implying that IL-17 and related genes may play important roles in the progression from HNPC to CRPC and from primary location to metastasis as well as in development of metastatic NEPC. AJCEU