Zhang Cheng, Han Yong, Huang Hao, Min Li, Qu Like, Shou Chengchao
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital and Institute, Beijing 100142, P.R. China.
Int J Oncol. 2014 Jun;44(6):2025-33. doi: 10.3892/ijo.2014.2352. Epub 2014 Mar 20.
Triple-negative breast cancer (TNBC) shows more aggressive clinical behavior and poorer outcome than non-triple-negative breast cancer (NTNBC), and cannot be treated either via endocrine therapy or by Trastuzumab. For TNBC, chemotherapy is currently the mainstay of systemic medical treatment, the lack of more efficient options of treatment has been a problem in breast cancer prevention. In this study, we aimed to find genes related to prognosis in TNBC by bioinformatic analysis and to provide therapeutic candidates for TNBC treatment. We compared the differences in gene expression levels between cancer patients and healthy individuals across five breast cancer microarray databases to generate a gene cohort specifically upregulated in the NTNBC subtype, whose expression levels are ≥2-fold higher in TNBC compared to NTNBC and healthy individuals. Another two databases with clinical information were applied for following Kaplan-Meier analysis, and high expression of BIRC5, CENPA and FAM64A in this cohort were found to be related to poor survival (OS, DMFS, DFS and RFS). This correlation was also seen in patients at early stages and grades. On the other hand, the outcome of patients with synchronous upregulation of these three genes was the worst, while those with synchronous low gene level was the best. In conclusion, BIRC5, CENPA and FAM64A are specifically upregulated in TNBC, and the high expression of these three genes is associated with poor breast cancer prognosis, suggesting their clinical implication as therapeutic targets in TNBC.
三阴性乳腺癌(TNBC)相较于非三阴性乳腺癌(NTNBC)表现出更具侵袭性的临床行为和更差的预后,并且无法通过内分泌治疗或曲妥珠单抗进行治疗。对于TNBC而言,化疗是目前全身药物治疗的主要手段,缺乏更有效的治疗选择一直是乳腺癌防治中的一个问题。在本研究中,我们旨在通过生物信息学分析找到与TNBC预后相关的基因,并为TNBC治疗提供候选治疗靶点。我们比较了五个乳腺癌微阵列数据库中癌症患者与健康个体之间的基因表达水平差异,以生成一个在NTNBC亚型中特异性上调的基因队列,该队列中基因在TNBC中的表达水平相较于NTNBC和健康个体高≥2倍。另外两个带有临床信息的数据库用于后续的Kaplan-Meier分析,结果发现该队列中BIRC5、CENPA和FAM64A的高表达与较差的生存率(总生存期、远处转移无进展生存期、无病生存期和无复发生存期)相关。这种相关性在早期和低级别患者中也可见。另一方面,这三个基因同步上调的患者预后最差,而这三个基因同步低表达的患者预后最好。总之,BIRC5、CENPA和FAM64A在TNBC中特异性上调,这三个基因的高表达与乳腺癌预后不良相关,提示它们作为TNBC治疗靶点的临床意义。