Background: Results of previous studies about the prognostic roles of histone H4 lysine 16 acetylation (H4K16ac) and histone H4 lysine 20 trimethylation (H4K20me3) in breast cancer were inconsistent. Cellular experiments revealed the interplays between H4K16ac and H4K20me3, but no population study explored the interaction between them on the prognosis.
Methods: H4K16ac and H4K20me3 levels in tumors were evaluated by immunohistochemistry for 958 breast cancer patients. Hazard ratios for overall survival (OS) and progression-free survival (PFS) were estimated using Cox regression models. Interaction was assessed on multiplicative scale. Concordance index (C-index) was calculated to verify the predictive performance.
Results: The prognostic roles of the low level of H4K16ac or H4K20me3 were significant only in patients with the low level of another marker and their interactions were significant. Moreover, compared with joint high levels of both them, only the combined low levels of both them was associated with a poor prognosis but not the low level of single one. The C-index of the clinicopathological model combined the joint expression of H4K16ac and H4K20me3 [0.739 for OS; 0.672 for PFS] was significantly larger than that of the single clinicopathological model [0.699 for OS, P < 0.001; 0.642 for PFS, P = 0.003] or the model combined with the single H4K16ac [0.712 for OS, P < 0.001; 0.646 for PFS, P < 0.001] or H4K20me3 [0.724 for OS, P = 0.031; 0.662 for PFS, P = 0.006].
Conclusions: There was an interaction between H4K16ac and H4K20me3 on the prognosis of breast cancer and the combination of them was a superior prognostic marker compared to the single one.
Keywords: Breast cancer; H4K16ac; H4K20me3; Histone modification; Prognosis.
© 2023. The Author(s) under exclusive licence to Japan Society of Clinical Oncology.