Lu Xiao-Feng, Zeng De, Liang Wei-Quan, Chen Chun-Fa, Sun Shu-Ming, Lin Hao-Yu
Department of Breast and Thyroid Surgery, The First Affiliated Hospital of Shantou University Medical College, Shantou, China.
Department of Medical Oncology, Cancer Hospital of Shantou University Medical College, Shantou, China.
Oncotarget. 2017 Dec 12;9(1):842-852. doi: 10.18632/oncotarget.23182. eCollection 2018 Jan 2.
Forkhead box protein M1(FoxM1) is a member of forkhead superfamily transcription factors. Emerging evidences have progressively contributed to our understanding on a central role of FoxM1 in human cancers. However, perspectives on the function of FoxM1 in breast cancer (BC) remain conflicting, and mostly were from basic research. Here, we explored the expression profile and prognostic values of FoxM1 based on analysis of pooled clinical datasets derived from online accessible databases, including , Breast Cancer Gene-Expression Miner v4.0, and Kaplan-Meier plotter. It was found that, FoxM1 mRNA expression was significantly higher in breast tumor versus normal control. FoxM1expression profile presented a distinct pattern in different molecular subtypes of BC patients. Higher expression of FoxM1 was correlated to low mRNA expression of estrogen receptor 1 (ESR1), erb-B2 receptor tyrosine kinase 2 (ERBB2), and was inversely associated with the expression of classical luminal regulators forkhead box protein A1 (FoxA1) and GATA binding protein 3 (GATA3). Elevated FoxM1 expression predicted shorter distance metastasis free survival (DMFS) in BC patients, particularly with estrogen receptor (ER) positive and Luminal A, Luminal B subtypes of BC. More interestingly, elevated FoxM1 expression predicted poor survival in breast cancer patients, especially in the ER (+), progesterone receptor (PR) (+) subgroups and BC patients received adjuvant chemotherapy only or treated with tamoxifen only. These results implied that FoxM1 is an essential prognostic factor and promising candidate target in the treatment of breast cancer.
叉头框蛋白M1（FoxM1）是叉头超家族转录因子的成员。越来越多的证据逐渐增进了我们对FoxM1在人类癌症中的核心作用的理解。然而，关于FoxM1在乳腺癌（BC）中的功能观点仍存在冲突，且大多来自基础研究。在此，我们基于对来自在线可访问数据库（包括乳腺癌基因表达挖掘器v4.0和Kaplan-Meier绘图仪）的汇总临床数据集的分析，探讨了FoxM1的表达谱和预后价值。研究发现，与正常对照相比，乳腺癌组织中FoxM1 mRNA表达显著更高。FoxM1的表达谱在BC患者的不同分子亚型中呈现出不同的模式。FoxM1的高表达与雌激素受体1（ESR1）、erb-B2受体酪氨酸激酶2（ERBB2）的低mRNA表达相关，并且与经典管腔调节因子叉头框蛋白A1（FoxA1）和GATA结合蛋白3（GATA3）的表达呈负相关。FoxM1表达升高预示着BC患者无远处转移生存期（DMFS）缩短，尤其是雌激素受体（ER）阳性以及BC的管腔A、管腔B亚型患者。更有趣的是，FoxM1表达升高预示着乳腺癌患者预后不良，尤其是在ER（+）、孕激素受体（PR）（+）亚组以及仅接受辅助化疗或仅接受他莫昔芬治疗的BC患者中。这些结果表明，FoxM1是乳腺癌治疗中一个重要的预后因素和有前景的候选靶点。
