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Mol Cancer. 2013 Jun 12;12:61. doi: 10.1186/1476-4598-12-61.

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

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  • 1Guangdong Lung Cancer Institute, 106 Zhongshan Er Rd, Guangzhou, 510080, China.

Abstract

BACKGROUND:

Aberrant 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.

RESULTS:

We 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 (χ2=15.81, P=0.001), smokers (χ2=8.92, P=0.004), patients with no lymph node involvement (χ2=5.14, P=0.029), and patients with early stage disease (χ2=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.

CONCLUSIONS:

Our 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.

PMID:
23758992
[PubMed - indexed for MEDLINE]
PMCID:
PMC3695801
Free PMC Article
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