乳腺癌中乙酰化转移酶P300和H3K56乙酰化蛋白表达与新辅助化疗及临床病理特征的相关性
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摘要
目的探讨乳腺癌中乙酰化转移酶P300和H3K56乙酰化(H3K56ac)蛋白表达与新辅助化疗及临床病理特征的相关性。方法应用免疫组化En Vision法检测57例乳腺癌组织化疗前、后及30例乳腺纤维腺病组织中P300和H3K56ac的表达。结果乳腺纤维腺病中P300和H3K56ac高表达率均高于化疗前乳腺癌组织(P<0.05)。化疗前P300表达与分子分型和肿瘤大小差异有显著性(P<0.05),HER-2阳性乳腺癌中P300高表达率较高(P<0.05),P300低表达时肿瘤直径较大(P<0.05)。化疗前P300表达与5年生存率差异有显著性,P300低表达提示预后较差(P<0.05)。化疗前后H3K56ac表达与乳腺癌临床病理特征差异无显著性(P>0.05);化疗后H3K56ac和P300高表达率显著高于化疗前(P<0.05);化疗前后两者蛋白表达均无明显相关性(P>0.05)。结论化疗前P300低表达时乳腺癌预后较差,可作为评估预后的风险因素。
Purpose To investigate the relationship between the expression of acetyltransferase P300 and H3 K56 acetylated protein with neoadjuvant chemotherapy and clinicopathological characteristics in breast carcinoma. Methods The expression of P300 and H3 K56 ac in 57 cases of before and after chemotherapy of breast cancer and 30 cases of breast fibroadenoma were detected by immunohistochemistry. Result The high expression of P300 and H3 K56 ac in breast fibroadenoma were significant higher than that in breast cancer tissues before chemotherapy( P < 0. 05). Before chemotherapy,the expression of P300 was significant correlated with molecular subtypes and tumor size( P < 0. 05),the high expression of P300 was significantly high in HER-2 positive type than that in other subtypes(P < 0. 05),the low expression of P300 protein was related with the larger tumor size( P < 0. 05). There was a significant differ-ence in P300 expression and 5 year survival rate before chemotherapy. The low expression of P300 protein was related with the poor prognosis( P < 0. 05). There was no significant difference between the expression of H3 K56 ac and the clinicopathological characteristics of breast cancer before and after chemotherapy( P> 0. 05). The high expression rates of H3 K56 ac and P300 in the tissues after chemotherapy was significantly higher than that in the tissues before chemotherapy( P < 0. 05). Also,there were no significant correlations with the expression of P300 and H3 K56 ac protein in the tissues before and after chemotherapy(P > 0. 05). Conclusion The low expression rate of P300 before chemotherapy companies with poor prognosis and could be a valuable prognostic marker for the breast cancer.
Purpose To investigate the relationship between the expression of acetyltransferase P300 and H3 K56 acetylated protein with neoadjuvant chemotherapy and clinicopathological characteristics in breast carcinoma. Methods The expression of P300 and H3 K56 ac in 57 cases of before and after chemotherapy of breast cancer and 30 cases of breast fibroadenoma were detected by immunohistochemistry. Result The high expression of P300 and H3 K56 ac in breast fibroadenoma were significant higher than that in breast cancer tissues before chemotherapy( P < 0. 05). Before chemotherapy,the expression of P300 was significant correlated with molecular subtypes and tumor size( P < 0. 05),the high expression of P300 was significantly high in HER-2 positive type than that in other subtypes(P < 0. 05),the low expression of P300 protein was related with the larger tumor size( P < 0. 05). There was a significant differ-ence in P300 expression and 5 year survival rate before chemotherapy. The low expression of P300 protein was related with the poor prognosis( P < 0. 05). There was no significant difference between the expression of H3 K56 ac and the clinicopathological characteristics of breast cancer before and after chemotherapy( P> 0. 05). The high expression rates of H3 K56 ac and P300 in the tissues after chemotherapy was significantly higher than that in the tissues before chemotherapy( P < 0. 05). Also,there were no significant correlations with the expression of P300 and H3 K56 ac protein in the tissues before and after chemotherapy(P > 0. 05). Conclusion The low expression rate of P300 before chemotherapy companies with poor prognosis and could be a valuable prognostic marker for the breast cancer.
引文
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[3]Gang X,Yang Y,Jian Z,et al.P300 acetyltransferase regulates fatty acid synthase expression,lipid metabolism and prostate cancer growth[J].Oncotarget,2016,7(12):15135-15149.
[4]刘标,周晓军.解读2012年WHO乳腺肿瘤分类[J].临床与实验病理学杂志,2012,28(11):1185-1187.
[5]Rotte A,Bhandaru M,Cheng Y,et al.Decreased expression of nuclear p300 is associated with disease progression and worse prognosis of melanoma patients.[J].PLo S One,2013,8(9):e75405.
[6]Vempati R K,Jayani R S,Notani D,et al.p300-mediated acetylation of histone H3 lysine 56 functions in DNA damage response in mammals[J].J Biol Chem,2010,285(37):28553.
[7]Ono H,Basson M D,Ito H.P300 inhibition enhances gemcitabine-induced apoptosis of pancreatic cancer[J].Oncotarget,2016,7(32):51301.
[8]Bhandaru M,Ardekani G S,Zhang G,et al.A combination of p300 and Braf expression in the diagnosis and prognosis of melanoma[J].BMC Cancer,2014,14(1):398.
[9]Jacobs K M,Misri S,Meyer B,et al.Unique epigenetic influence of H2AX phosphorylation and H3K56 acetylation on normal stem cell radioresponses[J].Mol Biol Cell,2016,27(8):1332-1345.