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与非小细胞肺癌生存相关的元基因。

Metagenes associated with survival in non-small cell lung cancer.

作者信息

Urgard Egon, Vooder Tõnu, Võsa Urmo, Välk Kristjan, Liu Mingming, Luo Cheng, Hoti Fabian, Roosipuu Retlav, Annilo Tarmo, Laine Jukka, Frenz Christopher M, Zhang Liqing, Metspalu Andres

机构信息

Department of Biotechnology, University of Tartu, 23 Riia, 51010 Tartu, Estonia.

出版信息

Cancer Inform. 2011;10:175-83. doi: 10.4137/CIN.S7135. Epub 2011 Jun 2.

Abstract

NSCLC (non-small cell lung cancer) comprises about 80% of all lung cancer cases worldwide. Surgery is most effective treatment for patients with early-stage disease. However, 30%-55% of these patients develop recurrence within 5 years. Therefore, markers that can be used to accurately classify early-stage NSCLC patients into different prognostic groups may be helpful in selecting patients who should receive specific therapies.A previously published dataset was used to evaluate gene expression profiles of different NSCLC subtypes. A moderated two-sample t-test was used to identify differentially expressed genes between all tumor samples and cancer-free control tissue, between SCC samples and AC/BC samples and between stage I tumor samples and all other tumor samples. Gene expression microarray measurements were validated using qRT-PCR.Bayesian regression analysis and Kaplan-Meier survival analysis were performed to determine metagenes associated with survival. We identified 599 genes which were down-regulated and 402 genes which were up-regulated in NSCLC compared to the normal lung tissue and 112 genes which were up-regulated and 101 genes which were down-regulated in AC/BC compared to the SCC. Further, for stage Ib patients the metagenes potentially associated with survival were identified.Genes that expressed differently between normal lung tissue and cancer showed enrichment in gene ontology terms which were associated with mitosis and proliferation. Bayesian regression and Kaplan-Meier analysis showed that gene-expression patterns and metagene profiles can be applied to predict the probability of different survival outcomes in NSCLC patients.

摘要

非小细胞肺癌(NSCLC)约占全球所有肺癌病例的80%。手术是早期疾病患者最有效的治疗方法。然而,这些患者中有30%-55%会在5年内复发。因此,可用于将早期NSCLC患者准确分类为不同预后组的标志物,可能有助于选择应接受特定治疗的患者。使用先前发表的数据集来评估不同NSCLC亚型的基因表达谱。采用适度的双样本t检验来鉴定所有肿瘤样本与无癌对照组织之间、鳞状细胞癌(SCC)样本与腺癌/大细胞癌(AC/BC)样本之间以及I期肿瘤样本与所有其他肿瘤样本之间差异表达的基因。使用定量逆转录聚合酶链反应(qRT-PCR)验证基因表达微阵列测量结果。进行贝叶斯回归分析和卡普兰-迈耶生存分析以确定与生存相关的元基因。我们鉴定出与正常肺组织相比在NSCLC中下调的599个基因和上调的402个基因,以及与SCC相比在AC/BC中上调的112个基因和下调的101个基因。此外,还鉴定出了与Ib期患者生存可能相关的元基因。在正常肺组织和癌组织之间表达不同的基因在与有丝分裂和增殖相关的基因本体术语中显示出富集。贝叶斯回归和卡普兰-迈耶分析表明,基因表达模式和元基因谱可用于预测NSCLC患者不同生存结果的概率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9f52/3118451/5b094c37e425/cin-1-2011-175f1.jpg

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