Clinical Pharmacology and New Drug Development Unit, European Institute of Oncology, Milan, Italy.
Pharmacogenomics J. 2010 Jun;10(3):180-90. doi: 10.1038/tpj.2009.53. Epub 2009 Nov 10.
The aim of this study was to investigate the influence of histology and site of analysis (primary tumor versus lymph node) on the expression of genes involved in gemcitabine and cisplatin activity in non-small-cell lung cancer (NSCLC). Excision repair cross-complementing-1 (ERCC1), human equilibrative nucleoside transporter-1 (hENT1), deoxycytidine kinase (dCK), 5'-nucleotidase (5'-NT), cytidine deaminase (CDA) and ribonucleotide-reductase regulatory subunits (RRM1 and RRM2) were analyzed by quantitative-reverse transcription-PCR in 88 microdissected samples from 69 chemonaive patients. The results showed different patterns of expression for all studied genes, suggesting a possible stratification of the patients. No difference was observed between primary tumor and lymph node metastasis, as well as in adenocarcinoma and squamous-cell carcinoma specimens, while we found a correlation between the CDA-A79C polymorphism and gene expression levels. These data suggest a similar genetic susceptibility to gemcitabine-cisplatin regimens for squamous cell and adenocarcinoma and support the use of both lymph node and primary tumor for the expression profiling of NSCLC.
本研究旨在探讨组织学和分析部位（原发肿瘤与淋巴结）对非小细胞肺癌（NSCLC）中吉西他滨和顺铂活性相关基因表达的影响。采用定量逆转录-PCR 法对 69 例未经化疗的 NSCLC 患者的 88 个微切割样本中的切除修复交叉互补基因 1（ERCC1）、人嘧啶核苷转运蛋白 1（hENT1）、脱氧胞苷激酶（dCK）、5'-核苷酸酶（5'-NT）、胞苷脱氨酶（CDA）和核糖核苷酸还原酶调节亚基（RRM1 和 RRM2）进行分析。结果显示，所有研究基因的表达模式均不同，提示患者可能存在分层。原发肿瘤与淋巴结转移、腺癌与鳞癌标本之间无差异，而 CDA-A79C 多态性与基因表达水平之间存在相关性。这些数据表明，鳞癌和腺癌对吉西他滨-顺铂方案具有相似的遗传易感性，并支持同时使用淋巴结和原发肿瘤进行 NSCLC 的表达谱分析。
