| Autor: |
Begum S; Department of Pathology, Johns Hopkins University, Baltimore, Maryland, 21231 USA., Hayashi M; Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, Maryland, 21231 USA., Ogawa T; Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, Maryland, 21231 USA., Jabboure FJ; Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, Maryland, 21231 USA., Brait M; Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, Maryland, 21231 USA., Izumchenko E; Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, Maryland, 21231 USA., Tabak S; Rosetta Genomics Ltd. 10 Plaut St., Rehovot, Israel, 76706., Ahrendt SA; Department of Surgery, Division of Surgical Oncology, University of Pittsburgh Medical Center, Pittsburgh, PA, 15213 USA., Westra WH; Department of Pathology, Johns Hopkins University, Baltimore, Maryland, 21231 USA., Koch W; Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, Maryland, 21231 USA., Sidransky D; Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, Maryland, 21231 USA., Hoque MO; Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University, Baltimore, Maryland, 21231 USA.; Department of Urology, Johns Hopkins University, Baltimore, Maryland, 21231 USA.; Department of Oncology, Johns Hopkins University, Baltimore, Maryland, 21231 USA. |
| Abstrakt: |
In spite of significant technical advances, genesis and progression of non-small cell lung cancer (NSCLC) remain poorly understood. We undertook an integrated genetic approach to discover novel microRNAs that were deregulated in NSCLCs. A total 119 primary NSCLCs with matched normal were analyzed for genome-wide copy number changes. We also tested a subset of matched samples by microRNA expression array, and integrated them to identify microRNAs positioned in allelic imbalance area. Our findings support that most of the identified deregulated microRNAs (miR-21, miR-23b, miR-31, miR-126, miR-150, and miR-205) were positioned in allelic imbalance areas. Among microRNAs tested in independent 114 NSCLCs, overexpression of miR-23b was revealed to be a significantly poor prognostic factor of recurrence free survival (HR = 2.40, P = 0.005, 95%CI: 1.32-4.29) and overall survival (HR = 2.35, P = 0.005, 95%CI: 1.30-4.19) in multivariable analysis. In addition, overexpression of miR-23b in H1838 cell line significantly increased cell proliferation, while inhibition of miR-23b in H1437 and H1944 cell lines significantly decreased cell doubling time. In summary, integration of genomic analysis and microRNA expression profiling could identify novel cancer-related microRNAs, and miR-23b could be a potential prognostic marker for early stage NSCLCs. Further biological studies of miR-23b are warranted for the potential development of targeted therapy. |
