利用Agilent定制基因芯片筛选相同病理类型、不同预后的早期乳腺癌的分子标记物

Screening molecular markers in early breast cancer of the same pathological types but with different prognoses using Agilent gene chip

目的分析相同病理类型、临床分期（I～Ⅱ期）但预后不同的乳腺癌组织的基因表达差异，筛选出有意义的基因组合，寻找与乳腺癌预后相关的基因，探索可以早期预测乳腺癌预后的基因分型诊断标准。方法用Agilent定制人8×15000芯片对筛选出的实验组8例早期乳腺癌患者的组织标本，结合其预后数据，进行差异基因表达分析；采用Real．timePCR技术，在同期收集的验证组42例乳腺癌样本中对差异表达的基因进行验证。结果基因芯片检测分析发现，实验组预后差样本比预后好样本有差异表达基因132个，其中44条基因显著上调，88条基因显著下调（差异均在2倍以上）。结论相同病理类型、临床分期、不同预后的早期乳腺癌组织中基因表达存在显著差异，CD44、MK167、NTRK2、Nek2、C160rf60、TOP2A、ANCCA、RRM2等8个基因可以作为早期乳腺癌预后预测基因标记物。

Objective： To screen molecular markers in early breast cancer and establish gene subtyping-based diagnostic criteria for predicting the prognosis of early breast cancers. Methods Tumor tissue specimens were obtained from 8 patients with early breast cancer for analysis of the differentially expressed genes using Agilent custom 8×15 000 chips in combination with the prognostic data of the patients. Another 42 tumor tissue specimens were used to validate the differential genes by real-time fluorescent quantitative PCR. Results Gene microarray analysis identified 132 differentially expressed genes between the patients with favorable and poor prognosis, and 44 of these genes were significantly up-regulated （by over two folds） and 88 down-regulated in patients with poor prognoses. Conclusion The gene expression profiles differ in early breast cancer tissues of the same pathological type but with different clinical stages and prognoses, and CD44, MKI67, NTRK2, Nek2, C16orf60, TOP2A, ANCCA, and RRM2 genes can be used as the prognostic markers for early breast cancer.