Variance in the expression of 5-fluorouracil pathway genes in colorectal cancer
Variance in the expression of 5-fluorouracil pathway genes in colorectal cancer
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DOI：
10.1158/1078-0432.ccr-04-1258
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发表时间：
2005-04-01
影响因子：
11.5
通讯作者：
McLeod, HL
中科院分区：
文献类型：
--
作者：
Kidd, EA;Yu, JS;McLeod, HL
尽管结直肠癌的死亡率位居第三，但治疗方法仍远未优化，患者对标准治疗的反应各异。药理学相关基因的分子差异可能导致反应的差异。本研究利用来自 52 名 Dukes C 结肠癌患者的配对非肿瘤和肿瘤样本，使用 Taqman PCR 来研究结直肠癌中 24 个 5-氟尿嘧啶 (5-FU) 通路基因的表达。在比较肿瘤组织与非恶性组织时，24 个基因中的 14 个显示出基因表达的显着变化。对于这些相同基因中的 11 个（FPGS、DHFR、GGH、NME1、NME2、RRM2、UMPH2、UNG、UMPS、TP53 和 TV），很大一部分患者在肿瘤组织中表现出特定基因的过度表达，肿瘤与非恶性 (T/N) 的比率 >1.2，而一种基因 (DPYD) 则相反，大量患者在肿瘤组织中表现出较低的表达（T/N < 0.8）。发现 5-FU 通路基因的多基因相关性，Spearman 等级相关性 >0.6（所有 P > 0.001），表明可能存在共调节机制。层次聚类分析至少创建了三组基因，这与其他统计方法的分组一致。此外，层次聚类根据基因表达显示了两组不同的患者。这些基因表达的变化可以为优化结直肠癌患者的治疗选择提供有价值的见解。
Although colorectal cancer has the third highest cancer mortality rate, the treatment remains far from optimized with patients showing variable responses to standard treatment. Molecular differences in pharmacologically relevant genes may contribute to the variability in response. This study used Taqman PCR to investigate the expression of 24 5-fluorouracil (5-FU) pathway genes in colorectal cancer using paired nontumor and tumor sample from 52 patients with Dukes' C colon cancer. In comparing tumor versus nonmalignant tissue, 14 of the 24 genes showed significant variation in gene expression. For 11 of these same genes (FPGS, DHFR, GGH, NME1, NME2, RRM2, UMPH2, UNG, UMPS, TP53, and TV), a significant proportion of the patients showed an over expression of the particular gene in tumor tissue with a tumor-to-nonmalignant (T/N) ratio >1.2, whereas one gene (DPYD) showed the converse with a large number of patients showing a lower expression in the tumor tissue (T/N < 0.8). Multiple gene correlations for the genes of the 5-FU pathway were found with the Spearman rank correlation of >0.6 (all P > 0.001), suggesting possible coregulation mechanisms. Hierarchical clustering analysis created at least three groups of genes, which were consistent with groupings by the other statistical methods. Additionally, the hierarchical clustering showed two distinct groups of patients based on their gene expression. These variations in gene expression could provide valuable insights for optimizing treatment selection for patients with colorectal cancer.