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细胞周期蛋白博拉在多种腺癌中作为一种新的不良预后因素。

Cell cycle protein Bora serves as a novel poor prognostic factor in multiple adenocarcinomas.

作者信息

Zhang Qiong-Xia, Gao Rui, Xiang Jin, Yuan Zhong-Yu, Qian Yuan-Min, Yan Min, Wang Zi-Feng, Liu Quentin, Zhao Hai-Dong, Liu Chang-Hong

机构信息

Sun Yat-Sen University Cancer Center, The Second Affiliated Hospital, Dalian Medical University, Dalian 116044, China.

Department of Oncology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510060, China.

出版信息

Oncotarget. 2017 Jul 4;8(27):43838-43852. doi: 10.18632/oncotarget.16631.

Abstract

Cell cycle protein Bora has been identified to integrate the functions of three major mitotic kinases: Cyclin-dependent kinase-1, Polo-like kinase-1, and Aurora A kinase. Overexpression of Bora disrupts spindle assembly and causes genomic instability. However, the clinical relevance of Bora in cancer remains unclear. In this study, we examined the expression of Bora and its association with clinical characteristics in breast (n = 538), lung (n = 144) and gastric (n = 77) adenocarcinomas. We found that Bora was overexpressed in primary breast cancer tissues compared to paired non-cancerous tissues. Bora overexpression was observed at a higher proportion in triple-negative breast cancer (TNBC, 77.63%) compared with non-TNBC subtypes (42.76%, P < 0.0001). Kaplan-Meier survival analysis indicated that Bora overexpression was associated with unfavourable overall survival (OS, P < 0.0001) and disease-free survival (DFS, P = 0.007) in breast cancer. In addition, Bora subclassified patients with distinct clinical outcomes in both stages (II/III) and subtypes (HR+, HER2+) of breast cancer. Consistently, Bora was associated with adverse prognosis in lung (P = 0.005 for OS and DFS P = 0.001 for DFS) and gastric adenocarcinomas (P < 0.0001 for OS, and P < 0.0001 for DFS). Moreover, Bora was positively correlated with proliferation index Ki67 in breast and gastric cancer (P < 0.001, P = 0.005, respectively). Multivariate analyses further revealed that Bora was an independent prognostic parameter for OS and DFS in all three types of adenocarcinomas. In conclusion, our findings demonstrated that Bora was overexpressed and served as an independent biomarker for poor prognosis in multiple adenocarcinomas.

摘要

细胞周期蛋白博拉已被确定可整合三种主要有丝分裂激酶的功能

细胞周期蛋白依赖性激酶-1、波罗样激酶-1和极光激酶A。博拉的过表达会破坏纺锤体组装并导致基因组不稳定。然而,博拉在癌症中的临床相关性仍不清楚。在本研究中,我们检测了博拉在乳腺(n = 538)、肺(n = 144)和胃(n = 77)腺癌中的表达及其与临床特征的关联。我们发现,与配对的非癌组织相比,原发性乳腺癌组织中博拉表达上调。与非三阴性乳腺癌亚型(42.76%,P < 0.0001)相比,三阴性乳腺癌(TNBC,77.63%)中观察到博拉过表达的比例更高。Kaplan-Meier生存分析表明,博拉过表达与乳腺癌患者不良的总生存期(OS,P < 0.0001)和无病生存期(DFS,P = 0.007)相关。此外,博拉在乳腺癌的两个阶段(II/III)和亚型(HR +、HER2 +)中均将患者分为具有不同临床结局的亚组。同样,博拉与肺癌(OS的P = 0.005,DFS的P = 0.001)和胃腺癌(OS的P < 0.0001,DFS的P < 0.0001)的不良预后相关。此外,博拉与乳腺癌和胃癌中的增殖指数Ki67呈正相关(分别为P < 0.001,P = 0.005)。多变量分析进一步显示,博拉是所有三种类型腺癌中OS和DFS的独立预后参数。总之,我们的研究结果表明,博拉在多种腺癌中表达上调,并作为不良预后的独立生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3361/5546444/867c5f5cb31d/oncotarget-08-43838-g001.jpg

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