Wan Guoxing, Tian Lin, Yu Yuandong, Li Fang, Wang Xuanbin, Li Chen, Deng Shouheng, Yu Xiongjie, Cai Xiaojun, Zuo Zhigang, Cao Fengjun
Department of Oncology, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei, China.
Department of Pathology, Renmin Hospital, Hubei University of Medicine, Shiyan 442000, Hubei, China.
Biochem Biophys Res Commun. 2017 Sep 9;491(1):104-111. doi: 10.1016/j.bbrc.2017.07.053. Epub 2017 Jul 11.
The present study was to evaluate the prognostic value of protein expression of Pofut1 and Notch1 signaling in breast cancer.
Formalin-fixed paraffin-embedded 314 breast specimens including 174 infiltrating ductal carcinoma(IDC), 50 ductal carcinoma in situ(DCIS) and 90 adjacent normal tissue(ANT) were immunohistochemically examined to evaluate the protein expression of Pofut1, activated Notch1(N1IC) and Slug on specimens. Survival analysis was performed by Kaplan-Meier method and Cox's proportional-hazards model. A online database was computationally used to further explore the prognostic role of Pofut1 and Notch1 mRNA expression by Kaplan-Meier Plotter.
Pofut1, Slug and N1IC expression were significantly increased in IDC compared to ANT(all p < 0.05). High expression of Pofut1, Slug and N1IC were associated with tumor aggressiveness including lymph node metastasis (LNM: p = 0.005 for Pofut1, p < 0.001 for N1IC, p = 0.017 for Slug), advanced stage(p = 0.039 for Pofut1, p = 0.025 for N1IC) and higher histological grade(p = 0.001 for N1IC). Additionally, high expression of Pofut1 was found to be significantly associated with high expressions of N1IC and Slug in IDC(r = 0.244, p = 0.001; r = 0.374, p < 0.001, respectively), similar correlation was also observed between high N1IC and Slug expression(r = 0.496, p < 0.001). Moreover, Kaplan-Meier and Cox's regression analysis indicated the significant prognostic value of elevated Pofut1, N1IC, Slug expressions, positive LNM and advanced tumor stage for the prediction of a shorter disease-free survival (DFS) and overall survival(OS). The web-based analysis also suggested a significant association of high Pofut1 and Notch1 mRNA expression with worse survival outcome.
Our findings suggested that overexpression of Pofut1 and activated Notch1 signaling may be associated with a poor prognosis in breast cancer.
本研究旨在评估Pofut1蛋白表达及Notch1信号通路在乳腺癌中的预后价值。
采用免疫组织化学方法检测314例福尔马林固定石蜡包埋的乳腺标本，其中包括174例浸润性导管癌（IDC）、50例原位导管癌（DCIS）和90例癌旁正常组织（ANT），以评估标本中Pofut1、活化的Notch1（N1IC）和Slug的蛋白表达。采用Kaplan-Meier法和Cox比例风险模型进行生存分析。通过在线数据库，利用Kaplan-Meier Plotter进一步探究Pofut1和Notch1 mRNA表达的预后作用。
与ANT相比，IDC中Pofut1、Slug和N1IC的表达显著增加（均p < 0.05）。Pofut1、Slug和N1IC的高表达与肿瘤侵袭性相关，包括淋巴结转移（LNM：Pofut1为p = 0.005，N1IC为p < 0.001，Slug为p = 0.017）、晚期（Pofut1为p = 0.039，N1IC为p = 0.025）和更高的组织学分级（N1IC为p = 0.001）。此外，在IDC中发现Pofut1的高表达与N1IC和Slug的高表达显著相关（r = 0.244，p = 0.001；r = 0.374，p < 0.001），N1IC和Slug的高表达之间也观察到类似的相关性（r = 0.496，p < 0.001）。此外，Kaplan-Meier和Cox回归分析表明，Pofut1、N1IC、Slug表达升高、阳性LNM和晚期肿瘤分期对预测较短的无病生存期（DFS）和总生存期（OS）具有显著的预后价值。基于网络的分析还表明，Pofut1和Notch1 mRNA高表达与较差的生存结果显著相关。
我们的研究结果表明，Pofut1的过表达和Notch1信号通路的激活可能与乳腺癌预后不良有关。
