Wei Wensong, Zou Yufeng, Jiang Qihua, Zhou Zhibin, Ding Haolong, Yan Liping, Yang Shixin
Department of Breast Cancer, The Third Hospital of Nanchang City, Nanchang, Jiangxi - PR China.
Int J Biol Markers. 2018 Jan;33(1):102-108. doi: 10.5301/ijbm.5000283.
Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, characterized by advanced disease stage and poor prognosis. Moreover, due to the lack of therapeutic markers, TNBC patients can't benefit fully from currently available targeted therapies.
To fully understand the molecular basis of TNBC, we used gene set enrichment analysis (GSEA) to screen out the most altered functional module in TNBC, from publicly available microarray data and studied the association of the candidate gene with TNBC development.
We found that the proteasome was significantly activated in TNBC. As compared with other breast cancer subtypes and normal tissue, proteasome subunit beta 5 (PSMB5), the key regulator of proteasome function, was overexpressed in TNBC tissue and predictive of poor prognosis. Moreover, we also found that PSMB5 knockdown induced TNBC apoptosis and significantly enhanced cancer cell sensitivity to the chemotherapeutic agents bortezomib and paclitaxel.
Our results suggest a potential role for PSMB5 as a biomarker and therapeutic target for TNBC.
三阴性乳腺癌(TNBC)是最具侵袭性的乳腺癌亚型,其特征为疾病分期较晚且预后较差。此外,由于缺乏治疗标志物,TNBC患者无法从目前可用的靶向治疗中充分获益。
为全面了解TNBC的分子基础,我们利用基因集富集分析(GSEA)从公开的微阵列数据中筛选出TNBC中变化最大的功能模块,并研究候选基因与TNBC发展的关联。
我们发现蛋白酶体在TNBC中显著激活。与其他乳腺癌亚型和正常组织相比,蛋白酶体功能的关键调节因子蛋白酶体亚基β5(PSMB5)在TNBC组织中过表达,且预示着预后不良。此外,我们还发现敲低PSMB5可诱导TNBC凋亡,并显著增强癌细胞对化疗药物硼替佐米和紫杉醇的敏感性。
我们的结果表明PSMB5作为TNBC的生物标志物和治疗靶点具有潜在作用。