Exploring the function of H3.3 in PC, we found that expression of two members of H3.3 chaperone complex HIRA (HIRA and UBN1), is increased in tumor compared with normal prostate tissue, is elevated in high/very high-risk PC groups (concordant with increased Gleason score), and their accumulation is associated with negative prognosis. This evidence concerns the gene HIRA and pachyonychia congenita.