Hub Genes in Non-Small Cell Lung Cancer Regulatory Networks.
Hub Genes in Non-Small Cell Lung Cancer Regulatory Networks.
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DOI：
10.3390/biom12121782
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发表时间：
2022-11-29
期刊：
影响因子：
5.5
通讯作者：
中科院分区：
文献类型：
--
作者：
目前，对于早期非小细胞肺癌(NSCLC)的最佳治疗选择，尚无准确的生物标志物。需要新的治疗靶点来改善非小细胞肺癌的生存结果。这项研究系统地评估了基因组规模调控网络中心性与早期非小细胞肺癌患者肿瘤发生、增殖和生存的关系。布尔隐含网络被用来使用患者DNA拷贝数变异、mRNA和蛋白质表达谱来构建多模式网络。肿瘤与非癌旁组织差异基因/蛋白表达的t统计、体外CRISPR-Cas9/RNA干扰(RNAi)筛查人类NSCLC细胞系的依赖分数、癌症基因组图谱(TCGA)NSCLC患者单变量COX模型中的风险比与图论中心性度量相关。在涉及基因/蛋白表达的多组学网络中，HUB基因与致癌、增殖潜力和患者较差的生存结果相关(p<；0.05，皮尔逊相关性)。在大多数构建的多组学网络中，免疫治疗靶点PD1、PDL1、CTLA4和CD27被列为第10个百分位数内的顶级枢纽基因。Bub3、DNM1L、EIF2S1、KPNB1、NMT1、PGAM1和STRAP是NSCLC增殖过程中重要的中枢基因，具有致癌潜力。这些结果支持HUB基因在非小细胞肺癌肿瘤发生、增殖和预后中的重要性，并暗示优先考虑治疗目标以改善患者的生存结果。
There are currently no accurate biomarkers for optimal treatment selection in early-stage non-small cell lung cancer (NSCLC). Novel therapeutic targets are needed to improve NSCLC survival outcomes. This study systematically evaluated the association between genome-scale regulatory network centralities and NSCLC tumorigenesis, proliferation, and survival in early-stage NSCLC patients. Boolean implication networks were used to construct multimodal networks using patient DNA copy number variation, mRNA, and protein expression profiles. T statistics of differential gene/protein expression in tumors versus non-cancerous adjacent tissues, dependency scores in in vitro CRISPR-Cas9/RNA interference (RNAi) screening of human NSCLC cell lines, and hazard ratios in univariate Cox modeling of the Cancer Genome Atlas (TCGA) NSCLC patients were correlated with graph theory centrality metrics. Hub genes in multi-omics networks involving gene/protein expression were associated with oncogenic, proliferative potentials and poor patient survival outcomes (p < 0.05, Pearson’s correlation). Immunotherapy targets PD1, PDL1, CTLA4, and CD27 were ranked as top hub genes within the 10th percentile in most constructed multi-omics networks. BUB3, DNM1L, EIF2S1, KPNB1, NMT1, PGAM1, and STRAP were discovered as important hub genes in NSCLC proliferation with oncogenic potential. These results support the importance of hub genes in NSCLC tumorigenesis, proliferation, and prognosis, with implications in prioritizing therapeutic targets to improve patient survival outcomes.
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影响因子：
2.7
作者：
Chang YC;Ding Y;Dong L;Zhu LJ;Jensen RV;Hsiao LL
通讯作者：
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11.2
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影响因子：
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通讯作者：
Muenz, Christian