A rapid bioinformatic method identifies novel genes with direct clinical relevance to colon cancer
A rapid bioinformatic method identifies novel genes with direct clinical relevance to colon cancer
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DOI：
10.1038/sj.onc.1204610
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发表时间：
2001-07-27
期刊：
影响因子：
8
通讯作者：
Schlag, PM
中科院分区：
文献类型：
--
作者：
Brett, D;Kemmner, W;Schlag, PM
识别差异表达影响原发性肿瘤手术后患者生存的基因是临床癌症研究的主要目标。为了解决这个问题，我们结合快速生物信息学搜索算法与定量RT-PCR在一组明确定义的结直肠癌病例详细的患者病史。编写了从Unigene EST集合的推定开放阅读框（ORF）中鉴定表达序列标签（EST）的搜索算法。计算每个Unigene ORF的健康组织与癌组织的表达比率。从生物信息学搜索中产生的前35个候选者在一组20个记录良好的结肠癌病例中检查mRNA表达。这35个基因中有4个与组织病理学参数显著相关。因此，在更大的患者队列中通过定量RT-PCR进一步分析它们的表达。Kaplan-Meier/log rank统计检验显示，在4个基因中的3个中，多达49名患者的基因表达与不良生存率显著相关。所有四个基因都与转移性肿瘤进展有很强的相关性。通过原位杂交将基因的表达定位于上皮细胞。
Identifying genes whose differential expression affect the survival of patients after primary tumor surgery is a major aim of clinical cancer research. To address this issue we combined rapid bioinformatic search algorithms with quantitative RT-PCR in a panel of clearly defined cases of colorectal carcinomas with detailed patient histories. Search algorithms were written that identified Expressed Sequence Tags (ESTs) from the Unigene EST collection of putative open reading frames (ORFs). Expression ratios of healthy to cancerous tissue of each Unigene ORF were calculated. The first 35 candidates arising from bioinformatic searches were examined for mRNA expression in a panel of 20 well documented cases of colon cancer. Four of these 35 genes showed significant correlations with histopathological parameters. Therefore, their expression was further analysed by quantitative RT-PCR in a larger patient cohort. Kaplan-Meier/log rank statistical tests of up to 49 patients in three of the four genes demonstrated significant association of gene expression with poor survival. All four genes demonstrated a strong association with metastatic tumor progression. Expression of the genes was localized to epithelial cells by in-situ hybridization.