Spindler Karen-Lise G, Nielsen Jens N, Ornskov Dorthe, Brandslund Ivan, Jakobsen Anders
Department of Oncology, Vejle Hospital, Kabbeltoft 25, 7100 Vejle, Denmark.
Acta Oncol. 2007;46(8):1113-7. doi: 10.1080/02841860701338853.
EGF/EGFR interactions are important mechanisms behind colorectal tumour development and growth. Recently a single nucleotide polymorphism in the EGF gene has been identified (EGF A61G). It may be a potential predictor for survival of patients receiving EGFR-inhibitor cetuximab treatment, but the clinical importance and the functional influence on EGF gene expression levels in colorectal cancer (CRC) patients have not yet been further assessed. The aim of the present study was to investigate the relationship between EGF A61G genotype and EGF gene expression levels in colorectal adenocarcinomas and normal colon tissue.
Eighty-one CRC patients were included in the study. Tissue samples from normal colon, adenocacinomas and corresponding blood samples were analysed by real-time PCR for EGF gene expression and EGF A61G genotype, respectively.
Thirty-three percent were AA, 48% and 19% A/G and G/G respectively. We found a significantly lower median age in the A/A group compared to the G/G group, suggesting a later time of diagnosis in the G/G patients. There was a significant difference between the median EGF gene expression among the three genotypes in normal colon (p < 0.001) but not in adenocarcinomas. Furthermore, the median EGF gene expression was lower in CRC tissue than in normal colon samples, (0.13 (range 0.01-6.4) vs. 0.76, (range 0.013-5.55)).
We suggest that EGF A61G genotype has a functional influence on EGF gene expression in normal colon in CRC patients. The clinical implications warrant further investigations in prospective trials.
表皮生长因子(EGF)/表皮生长因子受体(EGFR)相互作用是结直肠肿瘤发生和生长背后的重要机制。最近,在EGF基因中发现了一个单核苷酸多态性(EGF A61G)。它可能是接受EGFR抑制剂西妥昔单抗治疗患者生存的潜在预测指标,但尚未进一步评估其在结直肠癌(CRC)患者中的临床重要性及其对EGF基因表达水平的功能影响。本研究的目的是探讨EGF A61G基因型与结直肠腺癌及正常结肠组织中EGF基因表达水平之间的关系。
81例CRC患者纳入本研究。分别通过实时聚合酶链反应(PCR)对正常结肠、腺癌组织样本及相应血液样本进行EGF基因表达和EGF A61G基因型分析。
AA型占33%,A/G型占48%,G/G型占19%。我们发现A/A组的中位年龄显著低于G/G组,提示G/G组患者诊断时间较晚。正常结肠中三种基因型的EGF基因表达中位数存在显著差异(p<0.001),但在腺癌中无显著差异。此外,CRC组织中的EGF基因表达中位数低于正常结肠样本(0.13(范围0.01 - 6.4)对0.76,(范围0.013 - 5.55))。
我们认为EGF A61G基因型对CRC患者正常结肠中的EGF基因表达有功能影响。其临床意义值得在前瞻性试验中进一步研究。