代谢酶PFKFB4的高表达与可手术乳腺癌的不良预后相关。
High expression of metabolic enzyme PFKFB4 is associated with poor prognosis of operable breast cancer.
作者信息
Yao Ling, Wang Lei, Cao Zhi-Gang, Hu Xin, Shao Zhi-Ming
机构信息
1Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Fudan University, 270 Dong-An Rd., Shanghai, 200032 People's Republic of China.
2Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, People's Republic of China.
出版信息
Cancer Cell Int. 2019 Jun 18;19:165. doi: 10.1186/s12935-019-0882-2. eCollection 2019.
BACKGROUND
Enhanced 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.
METHODS
PFKFB4 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.
RESULTS
Kaplan-Meier survival analysis revealed that breast cancer patients with high PFKFB4 expression demonstrated unfavorable disease-free survival (= 0.008) and overall survival (= 0.002). PFKFB4 had an hazard ratio (HR) of 7.38 (95% CI 1.69-32.3; = 0.008) in univariate Cox analysis and retained prognostic power (HR 7.44, 95% CI 1.67-33.2; = 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.
CONCLUSIONS
Together, our findings establish the prognostic value of metabolic enzyme PFKFB4 in patients with operable breast cancer.
背景
肿瘤中增强的糖酵解作用，即瓦伯格效应，为癌细胞增殖和转移增强提供了代谢基础。瓦伯格途径酶6-磷酸果糖-2-激酶/果糖-2,6-二磷酸酶4（PFKFB4）是一种新发现的关键激酶，可调节转录重编程和细胞增殖。在此，我们展示了PFKFB4表达在可手术乳腺癌患者中的预后价值。
方法
通过免疫组织化学对从200例经组织学证实为浸润性导管癌的患者回顾性收集的手术标本中的PFKFB4表达进行评估。进行Kaplan-Meier生存分析和Cox回归分析以评估PFKFB4表达的预后意义。
结果
Kaplan-Meier生存分析显示，PFKFB4高表达的乳腺癌患者无病生存期（=0.008）和总生存期（=0.002）均较差。在单因素Cox分析中，PFKFB4的风险比（HR）为7.38（95%CI 1.69-32.3；=0.008），在根据肿瘤大小、淋巴结状态、分级、雌激素受体状态、人表皮生长因子受体2状态和亚型进行调整后，仍保留预后能力（HR 7.44，95%CI 1.67-33.2；=0.009），这表明PFKFB4是乳腺癌的独立预后因素。
结论
总之，我们的研究结果确立了代谢酶PFKFB4在可手术乳腺癌患者中的预后价值。
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