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Lead DEAD/H box helicase biomarkers with the therapeutic potential identified by integrated bioinformatic approaches in lung cancer
Computational and Structural Biotechnology Journal ( IF 6 ) Pub Date : 2020-12-28 , DOI: 10.1016/j.csbj.2020.12.007
Yuxin Cui , Adam Hunt , Zhilei Li , Emily Birkin , Jane Lane , Fiona Ruge , Wen G. Jiang

DEAD/H box helicases are implicated in lung cancer but have not been systematically investigated for their clinical significance and function. In this study, we aimed to evaluate the potential of DEAD/H box helicases as prognostic biomarkers and therapeutic targets in lung cancer by integrated bioinformatic analysis of multivariate large-scale databases. Survival and differential expression analysis of these helicases enabled us to identify four biomarkers with the most significant alterations. These were found to be the negative prognostic factors DDX11, DDX55 and DDX56, and positive prognostic factor DDX5. Pathway enrichment analysis indicates that MYC signalling is negatively associated with expression levels of the DDX5 gene while positively associated with that of DDX11, DDX55 and DDX56. High expression levels of the DDX5 gene is associated with low mutation levels of TP53 and MUC16, the two most frequently mutated genes in lung cancer. In contrast, high expression levels of DDX11, DDX55 and DDX56 genes are associated with high levels of TP53 and MUC16 mutation. The tumour-infiltrated CD8 + T and B cells positively correlate with levels of DDX5 gene expression, while negatively correlate with that of the other three DEAD box helicases, respectively. Moreover, the DDX5-associated miRNA profile is distinguished from the miRNA profiles of DDX11, DDX55 and DDX56, although each DDX has a different miRNA signature. The identification of these four DDX helicases as biomarkers will be valuable for prognostic prediction and targeted therapeutic development in lung cancer.



中文翻译:

领先的DEAD / H盒解旋酶生物标记物具有通过整合的生物信息学方法在肺癌中鉴定的治疗潜力

DEAD / H盒解旋酶与肺癌有关,但尚未对其临床意义和功能进行系统的研究。在这项研究中,我们旨在通过多变量大规模数据库的综合生物信息学分析评估DEAD / H盒解旋酶作为肺癌预后生物标志物和治疗靶标的潜力。这些解旋酶的存活和差异表达分析使我们能够鉴定出具有最显着改变的四个生物标记。发现这些是阴性预后因素DDX11,DDX55和DDX56,以及阳性预后因素DDX5。途径富集分析表明,MYC信号与DDX5基因的表达水平呈负相关,而与DDX11,DDX55和DDX56的表达正相关。DDX5基因的高表达水平与TP53和MUC16的低突变水平有关,这两个突变是肺癌中最常见的突变基因。相反,DDX11,DDX55和DDX56基因的高表达水平与TP53和MUC16突变的高水平相关。肿瘤浸润的CD8 + T和B细胞与DDX5基因表达水平呈正相关,而与其他三种DEAD盒解旋酶则呈负相关。此外,尽管每个DDX具有不同的miRNA签名,但与DDX5相关的miRNA图谱与DDX11,DDX55和DDX56的miRNA图谱有所区别。这四种DDX解旋酶作为生物标记物的鉴定对于肺癌的预后预测和靶向治疗的开发将是有价值的。肺癌中两个最常见的突变基因。相反,DDX11,DDX55和DDX56基因的高表达水平与TP53和MUC16突变的高水平相关。肿瘤浸润的CD8 + T和B细胞与DDX5基因表达水平呈正相关,而与其他三种DEAD盒解旋酶则呈负相关。此外,尽管每个DDX具有不同的miRNA签名,但与DDX5相关的miRNA图谱与DDX11,DDX55和DDX56的miRNA图谱有所区别。这四种DDX解旋酶作为生物标志物的鉴定对于肺癌的预后预测和靶向治疗的开发将是有价值的。肺癌中两个最常见的突变基因。相反,DDX11,DDX55和DDX56基因的高表达水平与TP53和MUC16突变的高水平相关。肿瘤浸润的CD8 + T和B细胞与DDX5基因表达水平呈正相关,而与其他三种DEAD盒解旋酶则呈负相关。此外,尽管每个DDX具有不同的miRNA签名,但与DDX5相关的miRNA图谱与DDX11,DDX55和DDX56的miRNA图谱有所区别。这四种DDX解旋酶作为生物标志物的鉴定对于肺癌的预后预测和靶向治疗的开发将是有价值的。肿瘤浸润的CD8 + T和B细胞与DDX5基因表达水平呈正相关,而与其他三种DEAD盒解旋酶则呈负相关。此外,尽管每个DDX具有不同的miRNA签名,但与DDX5相关的miRNA图谱与DDX11,DDX55和DDX56的miRNA图谱有所区别。这四种DDX解旋酶作为生物标记物的鉴定对于肺癌的预后预测和靶向治疗的开发将是有价值的。肿瘤浸润的CD8 + T和B细胞与DDX5基因表达水平呈正相关,而与其他三种DEAD盒解旋酶则呈负相关。此外,尽管每个DDX具有不同的miRNA签名,但与DDX5相关的miRNA图谱与DDX11,DDX55和DDX56的miRNA图谱有所区别。这四种DDX解旋酶作为生物标志物的鉴定对于肺癌的预后预测和靶向治疗的开发将是有价值的。

更新日期:2020-12-28
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