School of Medicine, Department of Genetics, Pamukkale University, Doktorlar Cad. Kat:3, Bayramyeri, Denizli, Turkey.
Mol Biol Rep. 2012 Jan;39(1):335-41. doi: 10.1007/s11033-011-0743-0. Epub 2011 May 7.
Excision Repair Cross-Complementing Group 1 (ERCC1) is an important DNA repair gene, playing critical role in nucleotide excision repair pathway and having a significant influence on genomic instability. Some studies support that ERCC1 might be a potential predictive and prognostic marker in non-small cell lung cancer (NSCLC). ERCC1 has also been shown to be a promising biomarker in NSCLC treated with a cisplatin-based regimen. Therefore, the determination of ERCC1 expression at DNA, mRNA and protein level in different stages of NSCLC is still an important topic in the cancer. Ninety-one formalin-fixed paraffin-embedded tumor samples histopathologically diagnosed as NSCLC were examined in this study. ERCC1 expression at protein level were scored by immunohistochemistry. The gene amplification and mRNA expression levels for ERCC1 were determined by real-time quantitative PCR. There was complete concordance among the three methods in 39 tumor samples (42.9%). A strong correlation was found between DNA amplification and mRNA expression (r=0.662) while there was no correlation between mRNA and protein assessment for ERCC1 expression (r=-0.013). ERCC1 expression at mRNA and DNA level (63.1 and 84.2%, respectively) in tumors at stage III was higher than at the other stages. In contrast, the protein expression at stage II and III (56.6 and 52.6%, respectively) of NSCLC was lower than that of tumors with stage I NSCLC. These results show that the mechanism by which ERCC1 expression might play a role in tumor behavior. This study was also confirmed that the appropriate validation and qualification in methods used for ERCC1 status were needed before its clinical application and implementation.
切除修复交叉互补基因 1(ERCC1)是一种重要的 DNA 修复基因,在核苷酸切除修复途径中起着关键作用,对基因组不稳定性有显著影响。一些研究支持 ERCC1 可能是非小细胞肺癌(NSCLC)的潜在预测和预后标志物。ERCC1 也已被证明是 NSCLC 中顺铂为基础的治疗方案的有前途的生物标志物。因此,在不同阶段的 NSCLC 中确定 ERCC1 在 DNA、mRNA 和蛋白质水平上的表达仍然是癌症研究的一个重要课题。本研究检测了 91 例福尔马林固定石蜡包埋的组织病理学诊断为 NSCLC 的肿瘤样本。采用免疫组织化学法对 ERCC1 蛋白水平的表达进行评分。采用实时定量 PCR 测定 ERCC1 的基因扩增和 mRNA 表达水平。在 39 例肿瘤样本中(42.9%),三种方法完全一致。DNA 扩增与 mRNA 表达之间存在很强的相关性(r=0.662),而 ERCC1 表达的 mRNA 和蛋白质评估之间没有相关性(r=-0.013)。III 期肿瘤中 ERCC1 在 mRNA 和 DNA 水平上的表达(分别为 63.1%和 84.2%)高于其他阶段。相比之下,II 期和 III 期 NSCLC 肿瘤的蛋白质表达(分别为 56.6%和 52.6%)低于 I 期 NSCLC 肿瘤。这些结果表明 ERCC1 表达可能在肿瘤行为中发挥作用的机制。本研究还证实,在临床应用和实施之前,需要对 ERCC1 状态所使用的方法进行适当的验证和资格认定。