Abstract: Objective To investigate prognostic value of HIST1H4F gene methylation in triple-negative breast cancer. Methods Thirty-one fresh breast cancer tissue samples and normal breast tissue samples were collected. After DNA extraction, bisulfite was used for methylation transformation. Fluorescence quantitative PCR was used to detect the methylation of HIST1H4F gene, and the difference of HIST1H4F gene methylation in cancer tissue samples and normal breast tissue was analyzed. The relationship between methylation of HIST1H4F gene and prognosis of triple-negative breast cancer was analyzed.At the same time, paraffin specimens of 37 cases of triple-negative breast cancer were collected, DNA was extracted and processed by the same method, and HIST1H4F gene methylation was detected to analyze the relationship between HIST1H4F gene methylation and prognosis of triple-negative breast cancer. Results The HIST1H4F methylation positive rates were 74.2% （23/31） in both normal and cancer tissues, and there was no significant difference between the two groups （χ²=0.000, P=1.000）. the HIST1H4F methylation positive rate in triple-negative breast cancer was higher than that in non-triple-negative breast cancer （93.8% vs. 53.3%, P=0.015）, HIST1H4F methylation-positive group had higher HIST1H4F grade Ⅲ and ER negative ratio than HIST1H4F methylation-negative group （60.9% vs. 12.5%, P=0.037; 69.6% vs. 25.0%, P=0.043）. For HIST1H4F methylation in paraffin tissue specimens of triple-negative breast cancer and found a HIST1H4F methylation positive rate of 27.0%,there was no significant difference between HIST1H4F methylation positive and negative groups in DFS （50.0% vs. 66.7%, χ²=1.141, P=0.285） and OS （90.0% vs. 96.3%, χ²=1.635, P=0.201）. Conclusion The positive rate of HIST1H4F gene methylation in triple negative breast cancer is high in fresh tissue samples, and histological grade Ⅲ and ER negative ratios were high in HIST1H4F gene methylation-positive breast cancer. While HIST1H4F methylation positive rate was low in paraffin tissue samples of triple-negative breast cancer. Whether HIST1H4F methylation is associated with triple-negative breast cancer prognosis remains to be determined and further studies are needed.

Key words: breast cancer, HIST1H4F, methylation

摘要： 目的 探讨HIST1H4F基因甲基化在三阴性乳腺癌中的意义。方法 收集31例乳腺癌新鲜的癌组织标本及正常乳腺组织标本,提取DNA后使用亚硫酸盐进行甲基化转化处理,荧光定量 PCR进行HIST1H4F基因甲基化检测,分析癌组织标本和正常乳腺组织中的HIST1H4F基因甲基化差异情况,并分析三阴性乳腺癌的HIST1H4F基因甲基化情况。同时收集37例三阴性乳腺癌的石蜡标本,提取DNA后同样方法处理再进行HIST1H4F基因甲基化检测,分析HIST1H4F基因甲基化与三阴性乳腺癌预后的关系。结果 新鲜组织标本中周围正常乳腺组织和癌组织中HIST1H4F甲基化阳性率均为74.2%（23/31）,两者的HIST1H4F甲基化阳性率无明显区别（χ²=0000,P=1.000）,分析发现三阴性乳腺癌组织中HIST1H4F甲基化阳性率高于非三阴性乳腺癌（93.8% vs. 53.3%,P=0.015）,HIST1H4F甲基化阳性乳腺癌的组织学分级Ⅲ级和ER阴性的乳腺癌中比率高于HIST1H4F甲基化阴性乳腺癌（60.9% vs. 12.5%,P=0.037;69.6% vs. 25.0%,P=0.043）。在三阴性乳腺癌的石蜡组织标本进行HIST1H4F甲基化检测,发现HIST1H4F甲基化阳性率为27.0%,且HIST1H4F甲基化阳性组和阴性组的DFS（50.0% vs. 66.7%,χ²=1.141,P=0.285）和OS（90.0% vs. 96.3%,χ²=1.635,P=0.201）在统计学上均无明显区别。结论 在新鲜组织标本中三阴性乳腺癌中检测HIST1H4F基因甲基化阳性率高,HIST1H4F基因甲基化阳性乳腺癌的组织学Ⅲ级和ER阴性比率高,而在三阴乳腺癌石蜡组织标本中检测的HIST1H4F甲基化阳性率较低,尚不能确定HIST1H4F甲基化与三阴性乳腺癌预后是否相关,仍有待于进一步研究。

关键词: 乳腺癌, HIST1H4F, 甲基化