Bjaanaes Maria Moksnes, Halvorsen Ann Rita, Solberg Steinar, Jørgensen Lars, Dragani Tommaso A, Galvan Antonella, Colombo Francesca, Anderlini Marco, Pastorino Ugo, Kure Elin, Børresen-Dale Anne-Lise, Brustugun Odd Terje, Helland Aslaug
Department of Genetics Institute for Cancer Research, Oslo University Hospital-The Norwegian Radium Hospital, Oslo, Norway; Department of Oncology, Oslo University Hospital-The Norwegian Radium Hospital, Oslo, Norway.
Int J Cancer. 2014 Oct 15;135(8):1812-21. doi: 10.1002/ijc.28828. Epub 2014 Mar 14.
The findings of mutations and the development of targeted therapies have improved lung cancer management. Still, the prognosis remains poor, and we need to know more about the genetic and epigenetic alterations in lung cancer. MicroRNAs are involved in crucial biological processes like carcinogenesis by regulating gene expression at the post-transcriptional level. In this project, we have studied the microRNA expression of lung adenocarcinomas and corresponding normal lung tissue and correlated the expression with clinical data and EGFR- and KRAS-mutational status. Agilent microarrays have been used, examining microRNA expression in 154 surgically resected lung adenocarcinomas and 20 corresponding normal lung tissue samples. Findings were confirmed by RT-qPCR in the same cohort and in an independent cohort of 103 lung cancer patients. EGFR and KRAS mutation analyses were also performed. 129 microRNAs were significantly differentially expressed in lung adenocarcinomas compared with normal lung tissue, and 17 microRNAs were differentially expressed between EGFR-mutated and EGFR wildtype tumors. We identified microRNAs associated with time to progression. We have identified several aberrantly expressed microRNAs that discriminate lung adenocarcinomas from normal lung tissue, and hence may be potential biomarkers for early detection. We have found microRNAs that are differentially expressed between EGFR-mutated and EGFR wildtype lung adenocarcinomas, suggesting that microRNAs can be used as molecular biomarkers in classification. We hypothesize that microRNA expression can be used as biomarkers for clinical course.
突变的发现以及靶向治疗的发展改善了肺癌的治疗。尽管如此，预后仍然很差，我们需要更多地了解肺癌中的基因和表观遗传改变。微小RNA通过在转录后水平调节基因表达参与致癌等关键生物学过程。在本项目中，我们研究了肺腺癌及相应正常肺组织的微小RNA表达，并将其表达与临床数据以及表皮生长因子受体（EGFR）和 Kirsten 大鼠肉瘤病毒癌基因（KRAS）突变状态相关联。我们使用了安捷伦微阵列，检测了154例手术切除的肺腺癌和20例相应正常肺组织样本中的微小RNA表达。在同一队列以及103例肺癌患者的独立队列中通过逆转录定量聚合酶链反应（RT-qPCR）对结果进行了验证。还进行了EGFR和KRAS突变分析。与正常肺组织相比，129种微小RNA在肺腺癌中显著差异表达，17种微小RNA在EGFR突变型和EGFR野生型肿瘤之间差异表达。我们鉴定出了与疾病进展时间相关的微小RNA。我们已经鉴定出几种异常表达的微小RNA，它们可将肺腺癌与正常肺组织区分开来，因此可能是早期检测的潜在生物标志物。我们发现了在EGFR突变型和EGFR野生型肺腺癌之间差异表达的微小RNA，这表明微小RNA可作为分类中的分子生物标志物。我们假设微小RNA表达可作为临床病程的生物标志物。
