Gain of 5p15.33 Is Associated with Progression of Bladder Cancer
Gain of 5p15.33 Is Associated with Progression of Bladder Cancer
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DOI：
10.1159/000111132
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发表时间：
2007-11
期刊：
影响因子：
3.5
通讯作者：
Yoshiaki Yamamoto;Y. Chochi;H. Matsuyama;S. Eguchi;S. Kawauchi;T. Furuya;A. Oga;J. Kang;K. Nait
中科院分区：
文献类型：
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作者：
Yoshiaki Yamamoto;Y. Chochi;H. Matsuyama;S. Eguchi;S. Kawauchi;T. Furuya;A. Oga;J. Kang;K. Nait
目的：寻找一种能区分高危和低危膀胱癌的生物学标志物。方法：采用由4,030个细菌人工染色体克隆组成的阵列比较基因组杂交(CGH)技术，对18例膀胱癌患者的全基因组拷贝数进行筛选。结果：在9例高级别膀胱癌中，5例(55.6%)检测到5p15.33基因的缺失，其中包括TPPP(微管蛋白聚合促进蛋白)和ZDHHC11(锌指DHHC结构域含蛋白11)基因，而在9例低级别膀胱癌中无一例表达。为证实初步数据，应用荧光原位杂交(FISH)对100例患者的5p15.33增益进行了研究，并将结果与生物学特性进行了比较。在FISH分析中，5p15.33的增加与较高的组织学分级(p<；0.0001)和较高的病理分期(p=0.0284)显著相关。获得5p15.33的肿瘤无进展生存率显著高于未获得5p15.33的肿瘤(p=0.0006，LOG-RANK检验)。多因素分析显示，5p15.33是膀胱癌疾病进展的预测因子(风险比：1.887，95%可信区间：1.215-2.968，p=0.0050)。结论：5p15.33(TPPP和ZDHHC11)基因的缺失可能成为鉴别膀胱癌进展的高危患者的潜在生物标志物。
Objective: To search for a biological marker to distinguish low-risk from high-risk bladder cancer indicating disease progression. Methods: The whole genome-wide copy numbers were screened in 18 patients with bladder cancer using array comparative genomic hybridization (CGH) consisting of 4,030 bacterial artificial chromosome clones. Results: Gain of 5p15.33, including TPPP (tubulin polymerization-promoting protein)and ZDHHC11 (zinc finger DHHC domain-containing protein 11) genes, was detected in 5 of 9 (55.6%) high-grade bladder cancers and no (0%; n = 9) low-grade bladder cancer. To confirm the preliminary data, 5p15.33 gain was studied by fluorescence in situhybridization (FISH) in 100 patients, and the results were compared with biological characteristics. In FISH analysis, gain of 5p15.33 was significantly correlated with higher histological grade (p < 0.0001) and advanced pathological stage (p = 0.0284). Tumors with a gain of 5p15.33 had a significantly higher progression-free survival rate than those without (p = 0.0006, log-rank test). Multivariate analysis revealed that gain of 5p15.33 was a predictor for disease progression in bladder cancer (hazard ratio: 1.887, 95% confidence interval: 1.215–2.968, p = 0.0050). Conclusion: These data suggest that gain of 5p15.33 (TPPP and ZDHHC11) may become a potential biomarker identifying high-risk patients with disease progression in bladder cancer.