Unique microRNA-profiles in EGFR-mutated lung adenocarcinomas

被引:71
作者
Bjaanaes, Maria Moksnes [1 ,2 ]
Halvorsen, Ann Rita [1 ]
Solberg, Steinar [3 ]
Jorgensen, Lars [3 ]
Dragani, Tommaso A. [4 ]
Galvan, Antonella [4 ]
Colombo, Francesca [4 ]
Anderlini, Marco [4 ]
Pastorino, Ugo [5 ]
Kure, Elin [1 ]
Rresen-Dale, Anne-Lise B. [1 ,6 ]
Brustugun, Odd Terje [1 ,2 ,6 ]
Helland, Aslaug [1 ,2 ,6 ]
机构
[1] Norwegian Radium Hosp, Dept Genet, Oslo Univ Hosp, Oslo, Norway
[2] Norwegian Radium Hosp, Dept Oncol, Oslo Univ Hosp, Oslo, Norway
[3] Univ Oslo, Rikshosp, Oslo Univ Hosp, Dept Cardiothorac Surg, N-0027 Oslo, Norway
[4] Fdn IRCCS Ist Nazl Tumori, Dept Predict & Prevent Med, Milan, Italy
[5] Fdn IRCCS Ist Nazl Tumori, Dept Thorac Surg, Milan, Italy
[6] Univ Oslo, Inst Clin Med, Fac Med, Oslo, Norway
关键词
microRNA; lung cancer; EGFR; survival; KRAS; GENE-EXPRESSION; BREAST-CANCER; SURVIVAL; PROGNOSIS; CARCINOMA; STAGE; OVEREXPRESSION; IDENTIFICATION; DYSREGULATION; PROGRESSION;
D O I
10.1002/ijc.28828
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
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.
引用
收藏
页码:1812 / 1821
页数:10
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