Clinical validity of the lung cancer biomarkers identified by bioinformatics analysis of public expression data
Clinical validity of the lung cancer biomarkers identified by bioinformatics analysis of public expression data
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DOI：
10.1158/0008-5472.can-07-0003
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发表时间：
2007-08-01
期刊：
影响因子：
11.2
通讯作者：
Lee, Sanghyuk
中科院分区：
文献类型：
--
作者：
Kim, Bumjin;Lee, Hyun Joo;Lee, Sanghyuk
分子标记物的鉴定通常导致重要的临床应用，例如早期诊断、预后和药物靶向。肺癌，癌症相关死亡的主要原因，仍然缺乏可靠的分子标志物。我们结合公开基因表达数据的生物信息学分析和临床验证来识别非小细胞肺癌的生物标志物基因。对基因表达的系列分析和表达序列标签数据进行荟萃分析，以产生肺癌差异表达基因的列表。通过仔细检查预测的基因，我们选择了20个基因进行实验验证，使用半定量逆转录酶-PCR。研究中使用的显微解剖临床标本包括三组：良性疾病的肺组织和非小细胞肺癌患者的配对（癌和病理正常）组织。经过广泛的统计分析，7个基因（CBLC，CYP 24 A1，ALDH 3A 1，AKRIB 10，S100 P，PLLWC和LOC 147166）被确定为潜在的诊断标志物。进行了定量实时PCR，以额外评估7个已鉴定基因的价值，从而确认至少2个基因（CBLC和CYP 24 A1）是高度可能的新型生物标志物。所鉴定的标记物的基因特性，特别是它们与肺癌和细胞信号传导通路调节的关系，进一步表明它们作为药物靶点的潜在价值。
Identification of molecular markers often leads to important clinical applications such as early diagnosis, prognosis, and drug targeting. Lung cancer, the leading cause of cancer-related deaths, still lacks reliable molecular markers. We have combined the bioinformatics analysis of the public gene expression data and clinical validation to identify biomarker genes for non-small-cell lung cancer. The serial analysis of gene expression and the expressed sequence tag data were meta-analyzed to produce a list of the differentially expressed genes in lung cancer. Through careful inspection of the predicted genes, we selected 20 genes for experimental validation using semiquantitative reverse transcriptase-PCR. The micro-dissected clinical specimens used in the study consisted of three groups: lung tissues from benign diseases and the paired (cancer and pathologic normal) tissues from non-small-cell lung cancer patients. After extensive statistical analyses, seven genes (CBLC, CYP24A1, ALDH3A1, AKRIB10, S100P, PLLWC, and LOC147166) were identified as potential diagnostic markers. Quantitative real-time PCR was carried out to additionally assess the value of the seven identified genes leading to the confirmation of at least two genes (CBLC and CYP24A1) as highly probable novel biomarkers. The gene properties of the identified markers, especially their relationship to lung cancer and cell signaling pathway regulation, further suggest their potential value as drug targets as well.