High expression of metabolic enzyme PFKFB4 is associated with poor prognosis of operable breast cancer
High expression of metabolic enzyme PFKFB4 is associated with poor prognosis of operable breast cancer
复制标题
代谢酶PFKFB4的高表达与可手术乳腺癌的不良预后相关
DOI：
10.1186/s12935-019-0882-2
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发表时间：
2019-06-18
影响因子：
5.8
通讯作者：
Shao, Zhi-Ming
中科院分区：
文献类型：
--
作者：
Yao, Ling;Wang, Lei;Shao, Zhi-Ming
背景肿瘤中糖酵解的增强，即所谓的瓦尔堡效应，为肿瘤细胞增殖和转移的增强提供了代谢基础。瓦尔堡途径酶6-磷酸果糖-2-激酶/果糖-2，6-二磷酸酶4（PFKFB 4）是一种新发现的调节转录重编程和细胞增殖的关键激酶。方法采用免疫组化方法检测200例经手术病理证实的浸润性导管乳腺癌患者手术切除标本中PFKFB 4的表达，并分析其与乳腺癌预后的关系。Kaplan-Meier生存分析和考克斯回归分析进行评估PFKFB 4表达的预后意义。结果Kaplan-Meier生存分析显示，与PFKFB 4高表达的乳腺癌患者表现出不利的无病生存（p= 0.008）和总生存（p= 0.002）。PFKFB 4的风险比（HR）为7.38（95% CI 1.69-32.3;p= 0.008），保留预后把握度（HR 7.44，95% CI 1.67-33.2; p= 0.009）当通过肿瘤大小、淋巴结状态、分级、雌激素受体状态、人表皮生长因子受体2状态和亚型调整时，结论PFKFB 4是乳腺癌的独立预后因子，其在乳腺癌手术患者中的预后价值值得进一步研究。
BackgroundEnhanced glycolysis in tumors, known as the Warburg effect, provides the metabolic basis of enhanced cancer cell proliferation and metastasis. The Warburg pathway enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 (PFKFB4) is a newly identified key kinase that regulates transcriptional reprogramming and cell proliferation. Here we show the prognostic value of PFKFB4 expression in patients with operable breast cancer.MethodsPFKFB4 expression was evaluated by immunohistochemistry in surgical specimens retrospectively collected from 200 patients with histologically proven invasive ductal breast cancer. Kaplan–Meier survival analysis and Cox regression analysis were performed to assess the prognostic significance of PFKFB4 expression.ResultsKaplan–Meier survival analysis revealed that breast cancer patients with high PFKFB4 expression demonstrated unfavorable disease-free survival (p= 0.008) and overall survival (p= 0.002). PFKFB4 had an hazard ratio (HR) of 7.38 (95% CI 1.69–32.3;p= 0.008) in univariate Cox analysis and retained prognostic power (HR 7.44, 95% CI 1.67–33.2;p= 0.009) when adjusted by tumor size, lymph node status, grade, estrogen receptor status, human epidermal growth factor receptor 2 status and subtype, which indicated PFKFB4 was an independent prognostic factor in breast cancer.ConclusionsTogether, our findings establish the prognostic value of metabolic enzyme PFKFB4 in patients with operable breast cancer.