Varied pathways of stage IA lung adenocarcinomas discovered by integrated gene expression analysis.
Varied pathways of stage IA lung adenocarcinomas discovered by integrated gene expression analysis.
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通过整合基因表达分析发现 IA 期肺腺癌的多种途径
DOI：
10.7150/ijbs.7.551
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发表时间：
2011-04-28
影响因子：
9.2
通讯作者：
Huang Y
中科院分区：
文献类型：
--
作者：
Chen C;Fu X;Zhang D;Li Y;Xie Y;Li Y;Huang Y
背景：发现肺腺癌（LAD）的进展相关基因和通路对了解肿瘤发生发展的分子机制具有重要意义。然而，很少有研究使用微阵列表达谱来关注肺腺癌发展过程中途径的变化。结果：我们对包含353例患者的4个LAD微阵列数据集进行了荟萃分析，以揭示正常肺组织与不同阶段LAD之间的差异表达基因（DEGs）。总共有1838个基因被发现异常，脂肪形成、昼夜节律和Id通路都发生了显著变化。有趣的是，大多数来自同一基因家族的基因（如白细胞介素受体、基质金属肽酶、组蛋白簇和小染色体维持复合物组分家族）被发现上调（或下调）。采用实时荧光定量PCR （Real-time PCR, qRT-PCR）对随机选取的18个deg在LAD细胞系中的表达进行验证。在不同阶段的通路分析中，氧化应激、糖酵解/糖异生和整合素介导的细胞粘附途径参与癌细胞的增殖和转移，在IA以外的其他阶段均受到显著调控。结论：参与脂肪形成和Id通路的基因可能在LADs的发生发展中起重要作用。基因家族成员的相似表达趋势提示在肿瘤进展中协同调控。三种途径（氧化应激、糖酵解/糖异生和整合素介导的细胞粘附途径）在IA期以外的其他阶段显著调节，这表明赋予侵袭性的基因和途径可能在侵袭前IB期被激活，而氧化应激和糖酵解/糖异生途径可能与顺铂化疗有很强的联系。IA期3条通路调节不显著，可能用于LAD的早期检测。
Background: Discovery of the progression-associated genes and pathways in lung adenocarcinoma (LAD) has important implications in understanding the molecular mechanism of tumor development. However, few studies had been performed to focus on the changes of pathways in lung adenocarcinoma development using microarray expression profile. Result: We performed a meta-analysis of 4 LAD microarray datasets encompassing 353 patients to reveal differentially expressed genes (DEGs) between normal lung tissues and LAD of different stages. Overall, 1 838 genes were found to be dys-regulated, and the adipogenesis, circadian rhythm, and Id pathways were significantly changed. Interestingly, most of the genes from the same gene family (such as Interleukin receptor, Matrix metallopeptidase, Histone cluster and Minichromosome maintenance complex component families) were found to be up-regulated (or down-regulated). Real-time PCR (qRT-PCR) was applied to validate the expression of randomly selected 18 DEGs in LAD cell lines. In the pathway analysis among stages, Oxidative stress, Glycolysis/Gluconeogenesis and Integrin-mediated cell adhesion pathways, which were involved in cancer cell proliferation and metastasis, were showed to be significantly regulated in stages other than IA. Conclusion: Genes involved in adipogenesis and Id pathways might play important roles in development of LADs. The similar trend of expression of the gene family members suggested coordinate regulation in tumor progression. Three pathways (Oxidative stress, Glycolysis/Gluconeogenesis and Integrin-mediated cell adhesion pathways) significantly regulated in stages other than stage IA suggested that genes and pathways conferring invasive character might be activated in the preinvasive stage IB, while the Oxidative stress and the Glycolysis/Gluconeogenesis pathways might have strong connections to cisplatin-based chemotherapy. The insignificantly regulated three pathways in stage IA might be used in early-stage detection of LAD.
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影响因子：
4.8
作者：
Chen, XY;Sievers, E;Conti, PS
通讯作者：
Conti, PS
影响因子：
3.8
作者：
Boudreau, Denise M.;Yu, Onchee;Daling, Janet R.
通讯作者：
Daling, Janet R.
影响因子：
3.5
作者：
Jafari, Peyman;Azuaje, Francisco
通讯作者：
Azuaje, Francisco
DOI：
10.1093/jnci/djn389
发表时间：
2008-12-03
期刊：
Journal of the National Cancer Institute
影响因子：
--
作者：
Jemal A;Thun MJ;Ries LA;Howe HL;Weir HK;Center MM;Ward E;Wu XC;Eheman C;Anderson R;Ajani UA;Kohler B;Edwards BK
通讯作者：
Edwards BK
影响因子：
64.8
作者：
Alizadeh, AA;Eisen, MB;Staudt, LM
通讯作者：
Staudt, LM