BCL11A overexpression predicts survival and relapse in non-small cell lung cancer and is modulated by microRNA-30a and gene amplificationReportar como inadecuado




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Molecular Cancer

, 12:61

First Online: 12 June 2013Received: 18 February 2013Accepted: 04 June 2013DOI: 10.1186-1476-4598-12-61

Cite this article as: Jiang, B., Zhang, X., Su, J. et al. Mol Cancer 2013 12: 61. doi:10.1186-1476-4598-12-61

Abstract

BackgroundAberrant activation of the proto-oncogene B-cell lymphoma-leukemia 11A BCL11A has been implicated in the pathogenesis of leukemia and lymphoma. However, the clinical significance of BCL11A in non-small cell lung cancer NSCLC remains unknown.

ResultsWe examined BCL11A expression at the protein and mRNA levels in a cohort n = 114 of NSCLC patients and assessed the relationship between BCL11A expression and clinicopathological parameters. Data from array-based Comparative Genomic Hybridization aCGH and microRNA transfection experiments were integrated to explore the potential mechanisms of abnormal BCL11A activation in NSCLC. Compared to adjacent non-cancerous lung tissues, BCL11A expression levels were specifically upregulated in NSCLC tissues at both the mRNA t = 9.81, P < 0.001 and protein levels. BCL11A protein levels were higher in patients with squamous histology χ = 15.81, P = 0.001, smokers χ = 8.92, P = 0.004, patients with no lymph node involvement χ = 5.14, P = 0.029, and patients with early stage disease χ = 3.91, P = 0.048. A multivariate analysis demonstrated that in early stage NSCLC IA–IIB, BCL11A was not only an independent prognostic factor for disease-free survival hazards ratio HR 0.24, 95% confidence interval CI 0.12-0.50, P < 0.001, but also for overall survival HR = 0.23, 95% CI 0.09-0.61, P = 0.003. The average BCL11A expression level was much higher in SCC samples with amplifications than in those without amplifications t = 3.30, P = 0.023. Assessing functionality via an in vitro luciferase reporter system and western blotting, we found that the BCL11A protein was a target of miR-30a.

ConclusionsOur results demonstrated that proto-oncogene BCL11A activation induced by miR-30a and gene amplification may be a potential diagnostic and prognostic biomarker for effective management of this disease.

KeywordsBCL11A Proto-oncogene Non-small cell lung cancer microRNA Prognosis Electronic supplementary materialThe online version of this article doi:10.1186-1476-4598-12-61 contains supplementary material, which is available to authorized users.

Ben-yuan Jiang, Xu-chao Zhang contributed equally to this work.

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Autor: Ben-yuan Jiang - Xu-chao Zhang - Jian Su - Wei Meng - Xue-ning Yang - Jin-ji Yang - Qing Zhou - Zhi-yong Chen - Zhi-hong 

Fuente: https://link.springer.com/



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