Impact of gene dosage on gene expression, biological processes and survival in cervical cancer: a genome-wide follow-up study.
Impact of gene dosage on gene expression, biological processes and survival in cervical cancer: a genome-wide follow-up study.
复制标题
基因剂量对宫颈癌的基因表达，生物学过程和存活的影响：全基因组随访研究。
DOI：
10.1371/journal.pone.0097842
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Berumen J
中科院分区：
文献类型：
--
作者：
Medina-Martinez I;Barrón V;Roman-Bassaure E;Juárez-Torres E;Guardado-Estrada M;Espinosa AM;Bermudez M;Fernández F;Venegas-Vega C;Orozco L;Zenteno E;Kofman S;Berumen J
我们研究了肿瘤拷贝数（CN）改变的基因组（CN-AG）在宫颈癌（CC）发生中的作用，特别是其对基因表达、生物学过程和患者生存的影响。59例人乳头瘤病毒16型（HPV 16）阳性的CC进行了研究与微阵列-31映射CN-AG和55个全球基因表达，与27个CC的共同点。研究了55例患者的5年生存率。缺失和扩增>2.5 Mb被定义为CN改变。CN-AG %范围为0 - 32.2%（平均值= 8.1±8.9）。 将肿瘤分类为低CN（平均值= 0.5±0.6，n = 11）、中等CN（平均值= 5.4±2.4，n = 10）或高CN（平均值= 19.2±6.6，n = 10）。 在3q中发现最高的%CN-AG，其平均贡献了所有CN改变的55%。在全基因组范围内，只有5.3%的CN改变基因直接由基因剂量解除调节。相比之下，完全重复的3q的比率是两倍。3q的扩增解释了整个肿瘤中23.2%的失调基因（r2 = 0.232，p = 0.006;方差分析），包括位于3q和其他染色体上的基因。 在高CN肿瘤中，共有862个基因被解除调控，但只有22.9%的CN改变。这表明，其余的基因不直接由基因剂量，但在反式由CN改变基因诱导的机制失调。后期促进复合物/细胞周期体（APC/C）依赖的蛋白酶体蛋白水解，糖酵解和细胞凋亡上调，而细胞粘附和血管生成下调专门在高CN肿瘤。高%CN-AG和APC/C依赖性蛋白酶体蛋白水解的上调基因表达谱与患者存活率差相关（p<0.05，对数秩检验）。沿着糖酵解，与FIGO分期呈线性相关（r>0.38，p<0.01，斯皮尔曼检验）。因此，抑制APC/C依赖的蛋白酶体蛋白水解和糖酵解可能有助于CC治疗。然而，它们是否对肿瘤生长不可或缺仍有待证明。
We investigated the role of tumor copy number (CN)–altered genome (CN-AG) in the carcinogenesis of cervical cancer (CC), especially its effect on gene expression, biological processes, and patient survival. Fifty-nine human papillomavirus 16 (HPV16)-positive CCs were investigated with microarrays–31 for mapping CN-AG and 55 for global gene expression, with 27 CCs in common. Five-year survival was investigated in 55 patients. Deletions and amplifications >2.5 Mb were defined as CN alterations. The %CN-AG varied from 0 to 32.2% (mean = 8.1±8.9). Tumors were classified as low (mean = 0.5±0.6, n = 11), medium (mean = 5.4±2.4, n = 10), or high (mean = 19.2±6.6, n = 10) CN. The highest %CN-AG was found in 3q, which contributed an average of 55% of all CN alterations. Genome-wide, only 5.3% of CN-altered genes were deregulated directly by gene dosage. In contrast, the rate in fully duplicated 3q was twice as high. Amplification of 3q explained 23.2% of deregulated genes in whole tumors (r2 = 0.232, p = 0.006; analysis of variance), including genes located in 3q and other chromosomes. A total of 862 genes were deregulated exclusively in high-CN tumors, but only 22.9% were CN altered. This suggests that the remaining genes are not deregulated directly by gene dosage, but by mechanisms induced in trans by CN-altered genes. Anaphase-promoting complex/cyclosome (APC/C)-dependent proteasome proteolysis, glycolysis, and apoptosis were upregulated, whereas cell adhesion and angiogenesis were downregulated exclusively in high-CN tumors. The high %CN-AG and upregulated gene expression profile of APC/C-dependent proteasome proteolysis were associated with poor patient survival (p<0.05, log-rank test). Along with glycolysis, they were linearly associated with FIGO stage (r>0.38, p<0.01, Spearman test). Therefore, inhibition of APC/C-dependent proteasome proteolysis and glycolysis could be useful for CC treatment. However, whether they are indispensable for tumor growth remains to be demonstrated.
登录
查看更多内容
影响因子：
21.3
作者：
Kawauchi, Keiko;Araki, Keigo;Tanaka, Nobuyuki
通讯作者：
Tanaka, Nobuyuki
影响因子：
3.7
作者：
Adamowicz, Martyna;Radlwimmer, Bernhard;Joos, Stefan
通讯作者：
Joos, Stefan
DOI：
10.1159/000056816
发表时间：
2000-01-01
期刊：
CYTOGENETICS AND CELL GENETICS
影响因子：
--
作者：
Atkin, NB
通讯作者：
Atkin, NB
影响因子：
8
作者：
Dowen, SE;Neutze, DM;Stanley, MA
通讯作者：
Stanley, MA
影响因子：
14.9
作者：
Huang, Da Wei;Sherman, Brad T.;Lempicki, Richard A.
通讯作者：
Lempicki, Richard A.