肺腺癌关键基因筛选及CDC20在肺腺癌中的表达
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南京医科大学科技发展基金(NMUB2018086)


Screening of key genes by bioinformatics analysis and the expression of CDC20 in lung adenocarcinoma
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    摘要:

    目的:筛选肺腺癌的关键基因,揭示肺腺癌潜在的分子机制。方法:利用3个肺腺癌相关基因芯片数据集,共包括156例肺腺癌和106例正常肺组织,进行肺腺癌潜在关键基因的筛选。结果:通过芯片数据分析得到341个重叠差异表达基因(differentially expressed gene,DEG),DEG主要富集的生物学过程是细胞外基质组织、调控化学激酶介导的信号通路、细胞对转化生长因子刺激的反应、细胞外基质组装、调控新生血管生成等。通过蛋白互作网络(protein protein interaction,PPI)筛选出10个关键基因,其中8个基因AURKA(aurora kinase A)、CDC20(cell division cycle 20)、CDH5(cadherin 5)、COL1α1(collagen Ⅰ,α1)、EDN1(endothelin 1)、MMP9(matrix metalloprotein 9)、PECAM1(platelet endothelial cell adhesion molecule 1)、SPP1(secreted phosphoprotein 1)与肺腺癌预后相关。其中CDC20与肺腺癌预后相关性最高,亚组分析发现,CDC20在肺腺癌各年龄段患者中的表达均明显高于正常组,CDC20在一期肺腺癌中表达低于二期、三期、四期,CDC20在腺泡型、实性为主型、混合型、透明细胞型表达高于其他亚型,CDC20在吸烟的肺腺癌患者中的表达低于不吸烟者。免疫组化检测显示CDC20在肺腺癌组织中表达明显高于正常肺组织,且腺泡型、实体型表达高于其他亚型。结论:CDC20在肺腺癌中高表达,且其高表达与肺腺癌的不良预后显著相关。CDC20有可能成为肺腺癌治疗的新靶点。

    Abstract:

    Objective:The aim of this study was to identify the key genes and uncover the potential molecular mechanisms of lung adenocarcinoma(LAC). Methods:In our study,three microarray data sets of LAC genes,including 156 cases of LAC and 106 cases of normal lung tissue,were used to screen the potential key genes. Results:First,341 overlapping differentially expressed genes(DEG)were found by microarray data analysis. The main biological processes of DEG enrichment were extracellular matrix tissue,regulation of chemical kinase-mediated signaling pathways,cell response to transformed growth factor stimulation,extracellular matrix assembly,and regulation of angiogenesis. Next,10 key genes were screened out by using protein protein interaction(PPI)network,including 8 genes AURKA(aurora kinase A),CDC20(cell division cycle 20),CDH5(cadherin 5),COL1α1(collagen I,α1),EDN1(endothelin 1),MMP9(matrix metalloprotein 9),PECAM1(platelet endothelial cell adhesion molecule 1),SPP1(secreted phosphoprotein 1),which were correlated with the prognosis of LAC. Additional,CDC20 has the highest correlationship with the prognosis of LAC. The subgroup analysis showed that expression of CDC20 in all age groups of LAC patients increased significantly compared with nomal control;expression of CDC20 in tumor stage Ⅰ is lower than tumor stage Ⅱ,Ⅲ,Ⅳ;expression of CDC20 in aciner subtype,solid subtype,mixed subtype,clear cell subtype was higher than other subtypes;expression of CDC20 in LAC patients with smoking was lower than the non-smokers. Furthermore,the results by immunohistochemical showed that expression of CDC20 in LAC tissues was significantly higher than that in normal lung tissues,in acinar subtype and solid subtype was higher than other subtypes. Conclusion:CDC20 is high expressed in LAC,which is correlated with poor prognosis of LAC. CDC20 might be a potential biomarker and therapeutic target for LAC.

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周春雷,韩 菲,樊祥山.肺腺癌关键基因筛选及CDC20在肺腺癌中的表达[J].南京医科大学学报(自然科学版),2020,(1):32-38

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  • 收稿日期:2019-04-11
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  • 在线发布日期: 2020-02-09
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