title: BCL11A overexpression predicts survival and relapse in non-small cell lung cancer and is modulated by microRNA-30a and gene amplification.
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.
authors.affiliation: Guangdong Lung Cancer Institute, 106 Zhongshan Er Rd, Guangzhou, 510080, China.
authors.forename: Ben-yuan
authors.initials: BY
authors.lastname: Jiang
authors.forename: Xu-chao
authors.initials: XC
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Su
authors.forename: Wei
authors.initials: W
authors.lastname: Meng
authors.forename: Xue-ning
authors.initials: XN
authors.lastname: Yang
authors.forename: Jin-ji
authors.initials: JJ
authors.lastname: Yang
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhou
authors.forename: Zhi-yong
authors.initials: ZY
authors.lastname: Chen
authors.forename: Zhi-hong
authors.initials: ZH
authors.lastname: Chen
authors.forename: Zhi
authors.initials: Z
authors.lastname: Xie
authors.forename: Shi-liang
authors.initials: SL
authors.lastname: Chen
authors.forename: Yi-long
authors.initials: YL
authors.lastname: Wu
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D000368:Aged; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D002460:Cell Line; D056915:DNA Copy Number Variations; D005260:Female; D005784:Gene Amplification; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012008:Recurrence; D012097:Repressor Proteins
chemical_list: D020413:3' Untranslated Regions; C486563:BCL11A protein, human; D002352:Carrier Proteins; C000715470:MAS1 protein, human; C546086:MIRN30b microRNA, human; D035683:MicroRNAs; D009687:Nuclear Proteins; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; D012097:Repressor Proteins