Increased BCAR1 predicts poor outcomes of non-small cell lung cancer in multiple-center patients.
Increased BCAR1 predicts poor outcomes of non-small cell lung cancer in multiple-center patients.
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BCAR1 增加预示多中心患者非小细胞肺癌的不良预后
DOI：
10.1245/s10434-013-3184-2
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发表时间：
2013-12
影响因子：
3.7
通讯作者：
Yang P
中科院分区：
文献类型：
--
作者：
Deng B;Sun Z;Jason W;Yang P
目的探讨多中心非小细胞肺癌（NSCLC）患者BCAR1表达的预后价值及其与临床人口学特征的关系。方法采用Mayo诊所77例腺癌的基因表达芯片（mRNA）、肿瘤基因组图谱（TCGA）中508例非小细胞肺癌的rna测序，以及大坪医院150例患者的bcar1蛋白表达免疫组化染色。在每个数据集中评估mRNA或蛋白表达与患者临床特征和总生存率的关系。我们还使用生物信息学预测工具预测了靶向BCAR1的microrna (miRNA)，并在TCGA数据集中的74例肺癌病例的miRNA测序数据中评估了miRNA与BCAR1表达的表达模式。结果在梅奥诊所的数据中，BCAR1-mRNA水平越高，肿瘤分期越晚期，淋巴转移越严重。在TCGA RNA-seq数据集中也观察到类似的变化。此外，TCGA数据集显示，较高的BCAR1-mRNA水平预示着腺癌和鳞状癌患者较差的生存率。有淋巴转移的腺癌患者的蛋白水平明显高于无转移的腺癌患者。肿瘤组织中BCAR1-mRNA的表达水平明显高于配对正常组织，但与配对正常组织中BCAR1-mRNA的表达水平无显著差异。在肿瘤中下调的mirna中，Let-7f-2和miR-22差异最大（P分别< 0.001和P= 0.007）。结论BCAR1表达升高预示NSCLC预后较差。我们推测BCAR1的mrna -蛋白解耦可能是肿瘤组织中特异性mirna抑制降低的结果，有待进一步研究。
ObjectiveThis study was designed to determine the prognostic value of BCAR1 expression and its associations with clinical-demographical characteristics in multiple centers of non-small cell lung cancer (NSCLC) patients.MethodsGene expression microarray (mRNA) of 77 adenocarcinomas from Mayo Clinic, RNA-sequencing of 508 NSCLC from The Cancer Genome Atlas (TCGA), and immunohistochemistry stain of BCAR1-protein expression in 150 cases from Daping Hospital were included in the study. The association of mRNA or protein expression with patient clinical characteristics and overall survival was assessed in each dataset. We also predicted microRNAs (miRNA) that target BCAR1 using bioinformatics prediction tools and evaluated miRNA expression patterns with BCAR1 expression in miRNA-sequencing data of 74 lung cancer cases from TCGA dataset.ResultsIn the Mayo Clinic dataset, a higher BCAR1-mRNA level correlated significantly with more advanced tumor-stage and lymphatic metastasis. Similar changes were observed in the TCGA RNA-seq dataset. Additionally, higher BCAR1-mRNA levels predicted poorer survival in adenocarcinoma and squamous carcinoma from the TCGA dataset. The protein levels in the adenocarcinoma cases with lymphatic metastasis were significantly higher than of those without metastasis. Tumor tissues demonstrated remarkably higher levels of protein compared with matched normal tissues although there was no significant difference in BCAR1-mRNA expression between tumor and matched normal tissues was detected. In miRNAs that were downregulated in the tumors, Let-7f-2 and miR-22 differed the most (P< 0.001 andP= 0.007, respectively).ConclusionsWe confirmed that increased BCAR1 expression predicts poorer prognosis in NSCLC. We postulate that mRNA-protein decoupling of BCAR1 may be a result of reduced inhibition of specific miRNAs in tumor tissues, which warrants further study.
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影响因子：
14.9
作者：
Maragkakis M;Vergoulis T;Alexiou P;Reczko M;Plomaritou K;Gousis M;Kourtis K;Koziris N;Dalamagas T;Hatzigeorgiou AG
通讯作者：
Hatzigeorgiou AG
影响因子：
10.3
作者：
Brinkman, A;van der Flier, S;Dorssers, LCJ
通讯作者：
Dorssers, LCJ
影响因子：
4.8
作者：
Kumbrink, Joerg;Kirsch, Kathrin H.
通讯作者：
Kirsch, Kathrin H.
影响因子：
4.8
作者：
Cabodi, Sara;Tinnirello, Agata;Defilippi, Paola
通讯作者：
Defilippi, Paola
影响因子：
14.9
作者：
Betel D;Wilson M;Gabow A;Marks DS;Sander C
通讯作者：
Sander C