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乳腺癌中 H3K4me3 和 H3K9ac 的表达。

Expression of H3K4me3 and H3K9ac in breast cancer.

机构信息

Department of Obstetrics and Gynecology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany.

Institute of Pathology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany.

出版信息

J Cancer Res Clin Oncol. 2020 Aug;146(8):2017-2027. doi: 10.1007/s00432-020-03265-z. Epub 2020 May 28.

Abstract

PURPOSE

Breast cancer is the leading cause of cancer death in females. Histone modifications have been shown to have an influence on the gene expression. This study focusses on the histone modifications H3K9ac and H3K4me3 in breast cancer and their impact on survival METHODS: H3K4me3 and H3K9ac expression was immunohistochemically examined in 235 tissue samples.

RESULTS

Positive estrogen receptor status was correlated with a higher IRS of the nuclear (p = 0.033), and of the cytoplasmic H3K4me3 staining (p = 0.009). H3K9ac intensity was associated to the Her2 status (p = 0.045) and to poor prognosis in cells with positive Ki67 status (p = 0.013). A high intensity of nuclear H3K4me3 staining was found to be correlated with a lower 10-year-survival (p = 0.026) and with lower breast cancer-specific survival (p = 0.004). High percentage score (> 190) of H3K9ac expression was correlated to worse breast cancer-specific survival (p = 0.005). Shorter progression-free survival was found in patients with nuclear (p = 0.013) and cytoplasmic H3K4me3expression (p = 0.024) and H3K9ac expression (p = 0.023).

CONCLUSION

This analysis provides new evidence of histone modifications in breast cancer. High H3K4me3 and H3K9ac expression was correlated with survival rates. Further investigation of histone modifications in breast cancer could lead to a more profound understanding of the molecular mechanisms of cancer development and could result in new therapeutic strategies.

摘要

目的

乳腺癌是女性癌症死亡的主要原因。组蛋白修饰已被证明对基因表达有影响。本研究专注于乳腺癌中的组蛋白修饰 H3K9ac 和 H3K4me3 及其对生存的影响。

方法

用免疫组织化学方法检测 235 个组织样本中的 H3K4me3 和 H3K9ac 表达。

结果

阳性雌激素受体状态与核内(p=0.033)和细胞质 H3K4me3 染色的 IRS 较高相关。H3K9ac 强度与 Her2 状态相关(p=0.045),与 Ki67 阳性细胞的预后不良相关(p=0.013)。核内 H3K4me3 染色强度高与 10 年生存率降低相关(p=0.026),与乳腺癌特异性生存率降低相关(p=0.004)。H3K9ac 表达的高百分比评分(>190)与乳腺癌特异性生存率降低相关(p=0.005)。核内(p=0.013)和细胞质 H3K4me3 表达(p=0.024)以及 H3K9ac 表达(p=0.023)的患者无进展生存期更短。

结论

本分析为乳腺癌中组蛋白修饰提供了新的证据。高 H3K4me3 和 H3K9ac 表达与生存率相关。进一步研究乳腺癌中的组蛋白修饰可能会深入了解癌症发展的分子机制,并可能导致新的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e037/11804352/1f7a24c90557/432_2020_3265_Fig1_HTML.jpg

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