A microarray-based gene expression analysis to identify diagnostic biomarkers for unknown primary cancer.

A microarray-based gene expression analysis to identify diagnostic biomarkers for unknown primary cancer.
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DOI:
10.1371/journal.pone.0063249
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Nishio K
Nishio K
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Kurahashi I;Fujita Y;Arao T;Kurata T;Koh Y;Sakai K;Matsumoto K;Tanioka M;Takeda K;Takiguchi Y;Yamamoto N;Tsuya A;Matsubara N;Mukai H;Minami H;Chayahara N;Yamanaka Y;Miwa K;Takahashi S;Takahashi S;Nakagawa K;Nishio K

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原发性不明癌症(CUP)在分子水平上的生物学基础仍然很大程度上是未知的,没有证据表明是否存在共同的生物学实体。在这里,我们评估了使用微阵列基因表达分析鉴定CUP的常见诊断生物标志物的可能性。使用Affytek U133 A Plus 2.0 GeneChip分析了60例CUP患者的肿瘤mRNA样本,并通过asinh(双曲反正弦)转换进行标准化,以构建CUP特异性的平均基因表达谱。使用公开的原始微阵列数据集构建了非CUP组特异性的基因表达谱。进行t检验以比较CUP与非CUP组,并选择具有最高倍数变化的前59个CUP特异性基因(p值<0.001)。在CUP组上调的44个基因中,鉴定出6个核糖体蛋白基因。已知这些基因中的两个(RPS 7和RPL 11)参与Mdm 2-p53途径。我们还鉴定了几个与转移和细胞凋亡相关的基因,表明CUP的生物学属性。本研究中鉴定的上调和下调基因的蛋白产物可能在临床上用作CUP的独特生物标志物。
The biological basis for cancer of unknown primary (CUP) at the molecular level remains largely unknown, with no evidence of whether a common biological entity exists. Here, we assessed the possibility of identifying a common diagnostic biomarker for CUP using a microarray gene expression analysis. Tumor mRNA samples from 60 patients with CUP were analyzed using the Affymetrix U133A Plus 2.0 GeneChip and were normalized by asinh (hyperbolic arc sine) transformation to construct a mean gene-expression profile specific to CUP. A gene-expression profile specific to non-CUP group was constructed using publicly available raw microarray datasets. The t-tests were performed to compare the CUP with non-CUP groups and the top 59 CUP specific genes with the highest fold change were selected (p-value<0.001). Among the 44 genes that were up-regulated in the CUP group, 6 genes for ribosomal proteins were identified. Two of these genes (RPS7 and RPL11) are known to be involved in the Mdm2–p53 pathway. We also identified several genes related to metastasis and apoptosis, suggesting a biological attribute of CUP. The protein products of the up-regulated and down-regulated genes identified in this study may be clinically useful as unique biomarkers for CUP.
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