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H4K16ac 和 H4K20me3 水平低与乳腺癌不良预后相关。

Combined low levels of H4K16ac and H4K20me3 predicts poor prognosis in breast cancer.

机构信息

Department of Epidemiology and Health Statistics, School of Public Health, Sun Yat-Sen University, 74 Zhongshan 2nd Rd, Guangzhou, 510080, Guangdong, China.

Department of Pathology, The Third Affiliated Hospital, Sun Yat-Sen University, 600 Tianhe Rd, Guangzhou, 510630, Guangdong, China.

出版信息

Int J Clin Oncol. 2023 Sep;28(9):1147-1157. doi: 10.1007/s10147-023-02378-y. Epub 2023 Jul 10.

DOI:10.1007/s10147-023-02378-y
PMID:37428307
Abstract

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.

摘要

背景

先前关于组蛋白 H4 赖氨酸 16 乙酰化(H4K16ac)和组蛋白 H4 赖氨酸 20 三甲基化(H4K20me3)在乳腺癌中的预后作用的研究结果不一致。细胞实验揭示了 H4K16ac 和 H4K20me3 之间的相互作用,但没有人群研究探索它们在预后方面的相互作用。

方法

对 958 例乳腺癌患者的肿瘤组织进行 H4K16ac 和 H4K20me3 水平的免疫组化评估。使用 Cox 回归模型估计总生存(OS)和无进展生存(PFS)的风险比。在乘法尺度上评估相互作用。计算一致性指数(C-index)以验证预测性能。

结果

仅在另一个标志物水平低的患者中,低水平的 H4K16ac 或 H4K20me3 的预后作用才有显著意义,并且它们的相互作用有显著意义。此外,与两者联合高水平相比,只有两者联合低水平与不良预后相关,而不是单个标志物低水平与不良预后相关。联合表达 H4K16ac 和 H4K20me3 的临床病理模型的 C-index[OS 为 0.739;PFS 为 0.672]明显大于单个临床病理模型[OS 为 0.699,P<0.001;PFS 为 0.642,P=0.003]或联合单个 H4K16ac[OS 为 0.712,P<0.001;PFS 为 0.646,P<0.001]或 H4K20me3[OS 为 0.724,P=0.031;PFS 为 0.662,P=0.006]的模型。

结论

H4K16ac 和 H4K20me3 在乳腺癌的预后中存在相互作用,两者联合比单个标志物更具有预后预测价值。

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