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【中国好声音】北大发现三阴性乳腺癌治疗新靶点

2022年07月19日

来源：SIBCS

三阴性乳腺癌对铂类和PARP抑制剂的敏感性与DNA同源重组缺陷密切相关，目前主要根据同源重组缺陷评分衡量同源重组缺陷，包括端粒等位基因失衡、大片段迁移和基因组杂合性丧失等。DNA解旋酶是通过同源重组修复DNA双链断裂过程不可或缺的组成部分，可利用ATP水解释放的能量解开双链DNA。

2022年7月9日，辛迪维旗下《医学计算数学方法》在线发表北京大学肿瘤医院龙孟平、刘毅强，北京大学人民医院刘宏军、吴金波、王殊、廖鑫、胡涛波学者的研究报告，发现了乳腺癌DNA解旋酶基因表达水平与肿瘤同源重组缺陷表现高度相关，并确定了由5个DNA解旋酶基因组成的基因特征可以高精度预测同源重组缺陷评分。

该研究利用癌症基因组图谱（TCGA）数据库871例乳腺癌组织的开源转录组和基因组数据，计算了22个DNA解旋酶基因表达水平与肿瘤同源重组缺陷评分的相关性。

结果发现，11个DNA解旋酶基因过表达与高同源重组缺陷评分相关，且在具有BRCA种系突变型或野生型乳腺癌都是如此。

此外，研究发现乳腺癌DNA同源重组缺陷评分可以通过5个DNA解旋酶基因的RNA表达量建立线性模型来预测。

因此，该研究结果表明，DNA解旋酶基因过表达可能与乳腺癌DNA同源重组缺陷表现高度相关，可以作为衡量同源重组修复状态的新工具以及治疗三阴性乳腺癌的新靶点。

参考文献

Comput Math Methods Med. 2022 Jul 9;2022:5508301.

Expression of DNA Helicase Genes Was Correlated with Homologous Recombination Deficiency in Breast Cancer.

Mengping Long, Hongjun Liu, Jinbo Wu, Shu Wang, Xin Liao, Yiqiang Liu, Taobo Hu.

Peking University Cancer Hospital, Beijing, China; Peking University People's Hospital, Beijing, China.

Homologous recombination deficiency which is currently measured by the homologous recombination deficiency (HRD) score including score of telomeric allelic imbalance (TAI), large-scale transition (LST), and loss of heterozygosity (LOH) is highly related with sensitivity to platinum-containing drug and PARP inhibitors. DNA helicases are essential components for the homologous recombination repair process in which DNA helicases unwind double-strand DNA utilizing ATP hydrolysis. In our study, the correlation between the expression of DNA helicase genes and HRD score in breast cancer was analyzed. The overexpression in half of the DNA helicase genes was found to be highly correlated with a high HRD score both in BRCA-mutated and BRCA wild-type breast cancer. Moreover, HRD score can be predicted by a linear function contributed by five DNA helicase genes. In conclusion, our study revealed a close relation between the overexpression of certain DNA helicase genes and the deficiency of homologous recombination repair in breast cancer.

DOI: 10.1155/2022/5508301