BCL11A overexpression predicts survival and relapse in non-small cell lung cancer and is modulated by microRNA-30a and gene amplification.
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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BCL11A 过表达可预测非小细胞肺癌的生存和复发，并受到 microRNA-30a 和基因扩增的调节
DOI：
10.1186/1476-4598-12-61
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发表时间：
2013-06-12
期刊：
影响因子：
37.3
通讯作者：
Wu YL
中科院分区：
文献类型：
--
作者：
Jiang BY;Zhang XC;Su J;Meng W;Yang XN;Yang JJ;Zhou Q;Chen ZY;Chen ZH;Xie Z;Chen SL;Wu YL
研究背景原癌基因B细胞淋巴瘤/白血病11A（BCL11A）的异常激活与白血病和淋巴瘤的发病机制有关。然而，BCL 11 A在非小细胞肺癌（NSCLC）的临床意义仍然unknown. ResultsWe研究BCL 11 A的表达在蛋白质和mRNA水平在一个队列（n = 114）的NSCLC患者和评估BCL 11 A的表达和临床病理参数之间的关系。整合基于阵列的比较基因组杂交（aCGH）和microRNA转染实验的数据，以探索NSCLC中异常BCL 11 A激活的潜在机制。与癌旁肺组织相比，NSCLC组织中BCL 11A的表达在mRNA和蛋白水平均显著上调（t = 9.81，P <0.001）。BCL 11A蛋白表达在鳞癌（χ 2 = 15.81，P = 0.001）、吸烟者（χ 2 = 8.92，P = 0.004）、无淋巴结转移者（χ 2 = 5.14，P = 0.029）和早期病变者（χ 2 = 3.91，P = 0.048）中均较高。多因素分析显示，BCL 11 A不仅是影响早期非小细胞肺癌（IA-Ⅱ B）患者无病生存期（HR = 0.24，95%CI 0.12-0.50，P <0.001）和总生存期（HR = 0.23，95%CI 0.09-0.61，P = 0.003）的独立预后因素。扩增组的BCL 11A平均表达水平明显高于未扩增组（t = 3.30，P = 0.023）。结论miR-30 a可诱导原癌基因BCL 11 A的激活和基因扩增，这可能是一种潜在的诊断和预后生物标志物，可用于有效治疗该病。
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 (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 anin vitroluciferase reporter system and western blotting, we found that the BCL11A protein was a target of miR-30a.ConclusionsOur results demonstrated that proto-oncogeneBCL11Aactivation induced by miR-30a and gene amplification may be a potential diagnostic and prognostic biomarker for effective management of this disease.
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影响因子：
11.2
作者：
Reddy SD;Pakala SB;Ohshiro K;Rayala SK;Kumar R
通讯作者：
Kumar R
影响因子：
64.8
作者：
通讯作者：
--
DOI：
10.1016/j.bbrc.2007.02.003
发表时间：
2007-04-06
影响因子：
3.1
作者：
Kamimura, Kenya;Ohi, Hiroyuki;Kominami, Ryo
通讯作者：
Kominami, Ryo
影响因子：
6.4
作者：
Schmelz, K;Wagner, M;Tamm, I
通讯作者：
Tamm, I
影响因子：
64.5
作者：
Lewis, BP;Shih, IH;Burge, CB
通讯作者：
Burge, CB