Overexpression of Uridine-Cytidine Kinase 2 Correlates with Breast Cancer Progression and Poor Prognosis.
Overexpression of Uridine-Cytidine Kinase 2 Correlates with Breast Cancer Progression and Poor Prognosis.
复制标题
尿苷胞苷激酶 2 的过度表达与乳腺癌进展和不良预后相关
DOI：
10.4048/jbc.2017.20.2.132
复制
发表时间：
2017-06
影响因子：
2.4
通讯作者：
Yen Y
中科院分区：
文献类型：
--
作者：
Shen G;He P;Mao Y;Li P;Luh F;Ding G;Liu X;Yen Y
目的尿苷胞苷激酶（UCK）2是嘧啶核苷酸生物合成补救途径的限速酶。最近的研究表明，UCK 2在许多类型的癌症中过表达，并可能在激活人类癌细胞中的抗肿瘤前药中发挥关键作用。在本研究中，我们评估了UCK 2在乳腺癌中的潜在预后价值。方法检索公共数据库，探讨UCK 2基因表达与乳腺癌患者临床参数之间的关系。进行基因集富集分析（GSEA）以鉴定与UCK 2基因表达水平相关的生物学途径。使用10个独立的大规模乳腺癌微阵列数据集进行生存分析。结果UCK 2 mRNA在乳腺癌组织中的表达明显高于癌旁组织和正常乳腺组织。高UCK 2水平与雌激素受体阴性（p<0.001）、晚期肿瘤分级（p<0.001）和低肿瘤分化（p<0.001）相关。GSEA显示，UCK 2高乳腺癌富集与转移、祖细胞样表型和预后不良相关的基因集。微阵列数据集的多变量考克斯比例风险回归分析证实，高UCK 2基因表达以剂量反应方式与总生存率相关。UCK 2的预后能力上级于TNM分期，与多基因标记的预后能力相当。结论UCK 2有可能成为乳腺癌患者的一个有前景的预后生物标志物。
Purpose Uridine-cytidine kinase (UCK) 2 is a rate-limiting enzyme involved in the salvage pathway of pyrimidine-nucleotide biosynthesis. Recent studies have shown that UCK2 is overexpressed in many types of cancer and may play a crucial role in activating antitumor prodrugs in human cancer cells. In the current study, we evaluated the potential prognostic value of UCK2 in breast cancer. Methods We searched public databases to explore associations between UCK2 gene expression and clinical parameters in patients with breast cancer. Gene set enrichment analysis (GSEA) was performed to identify biological pathways associated with UCK2 gene expression levels. Survival analyses were performed using 10 independent large-scale breast cancer microarray datasets. Results We found that UCK2 mRNA expression was elevated in breast cancer tissue compared with adjacent nontumorous tissue or breast tissue from healthy controls. High UCK2 levels were correlated with estrogen receptor negativity (p<0.001), advanced tumor grade (p<0.001), and poor tumor differentiation (p<0.001). GSEA revealed that UCK2-high breast cancers were enriched for gene sets associated with metastasis, progenitor-like phenotypes, and poor prognosis. Multivariable Cox proportional hazards regression analyses of microarray datasets verified that high UCK2 gene expression was associated with poor overall survival in a dose-response manner. The prognostic power of UCK2 was superior to that of TNM staging and comparable to that of multiple gene signatures. Conclusion These findings suggest that UCK2 may be a promising prognostic biomarker for patients with breast cancer.
登录
查看更多内容
影响因子：
3.8
作者：
Esserman, Laura J.;Berry, Donald A.;Cheang, Maggie C. U.;Yau, Christina;Perou, Charles M.;Carey, Lisa;DeMichele, Angela;Gray, Joe W.;Conway-Dorsey, Kathleen;Lenburg, Marc E.;Buxton, Meredith B.;Davis, Sarah E.;van't Veer, Laura J.;Hudis, Clifford;Chin, Koei;Wolf, Denise;Krontiras, Helen;Montgomery, Leslie;Tripathy, Debu;Lehman, Constance;Liu, Minetta C.;Olopade, Olufunmilayo I.;Rugo, Hope S.;Carpenter, John T.;Livasy, Chad;Dressler, Lynn;Chhieng, David;Singh, Baljit;Mies, Carolyn;Rabban, Joseph;Chen, Yunni-Yi;Giri, Dilip;Au, Alfred;Hylton, Nola
通讯作者：
Hylton, Nola
DOI：
10.1111/j.1349-7006.2002.tb01325.x
发表时间：
2002-07
期刊：
Japanese journal of cancer research : Gann
影响因子：
--
作者：
Shimamoto Y;Koizumi K;Okabe H;Kazuno H;Murakami Y;Nakagawa F;Matsuda A;Sasaki T;Fukushima M
通讯作者：
Fukushima M
影响因子：
168.9
作者：
Wang, YX;Klijn, JGM;Foekens, JA
通讯作者：
Foekens, JA
影响因子：
3.6
作者：
Van Rompay, AR;Norda, A;Karlsson, A
通讯作者：
Karlsson, A
影响因子：
3.8
作者：
Itoh, Mitsuya;Iwamoto, Takayuki;Pusztai, Lajos
通讯作者：
Pusztai, Lajos