Multi-omics analysis at epigenomics and transcriptomics levels reveals prognostic subtypes of lung squamous cell carcinoma.
Multi-omics analysis at epigenomics and transcriptomics levels reveals prognostic subtypes of lung squamous cell carcinoma.
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DOI：
10.1016/j.biopha.2020.109859
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发表时间：
2020-02
期刊：
影响因子：
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通讯作者：
Yong Xu;Y. She;Yaqiang Li;Hao Li;Zihao Jia;G. Jiang;Leilei Liang;L. Duan
中科院分区：
文献类型：
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作者：
Yong Xu;Y. She;Yaqiang Li;Hao Li;Zihao Jia;G. Jiang;Leilei Liang;L. Duan
在这项研究中，我们通过整合多组DNA拷贝数变异（CNV）和甲基化变异（MET）数据，并进行qPCR和免疫组化鉴定，确定了肺鳞状细胞癌（LUSC）的预后生物标志物。我们检测了368例LUSC患者中CNV和MET的表达。确定了与DNA拷贝数或DNA甲基化相关的基因表达，并基于这些相关性定义了四种LUSC基因亚型。iC 1亚型的预后总生存期（OS）明显低于iC 2和iC 4亚型。我们评估了每个亚型的免疫评分，发现iC 3亚型的六种免疫细胞评分显著高于其他亚型（p < 0.01）。通过比较CNV和MET在亚型中的表达，确定了三个与预后相关的基因，NFE 2L 2，ASAH 2和RIMBP 2。亚型之间的突变差异分析揭示了一组基因之间的iC 1和iC 4亚型的显着突变。LUSC中NFE 2L 2基因突变数显著高于其他基因，该基因具有预后意义。最佳iC 4亚型的突变数量显著高于预后最差的iC 1亚型;另外两个基因ASAH 2和RIMBP 2仅在预后最差的iC 1亚型中发现。这种对基因组学、表观基因组学和转录组学数据的全面多组学分析为LUSC的分子机制提供了新的见解，并可能有助于识别用于早期疾病诊断的生物分子标记物。
In this study, we identified prognostic biomarkers for lung squamous cell carcinoma (LUSC) by integrating multiple sets of DNA copy number variants (CNV) and methylation variant (MET) data, and performing qPCR and immunohistochemical identification. We examined the expression of CNV and MET in 368 LUSC patients. Gene expression associated with DNA copy number or DNA methylation was identified and four LUSC gene subtypes were defined based on these correlations. The prognosis overall survival (OS) of the iC1 subtype was significantly lower than that in the iC2 and iC4 subtypes. We assessed the immune scores of each subtype and found that the six immune cell scores of the iC3 subtype were significantly higher than the other subtypes (p < 0.01). Three genes associated with prognosis, NFE2L2, ASAH2, and RIMBP2, were identified by comparing the expression of CNV and MET in subtypes. Analysis of mutational differences between subtypes revealed a group of genes with significant mutations between the iC1 and iC4 subtypes. The number of mutations in the NFE2L2 gene in LUSC was significantly higher than that in other genes, and the gene was prognostic. The number of mutations was significantly higher in the best iC4 subtype than the iC1 subtype with the worst prognosis; the other two genes, ASAH2 and RIMBP2, were only found in the worst prognosis of the iC1 subtype. This comprehensive multi-omics analysis of genomics, epigenomics, and transcriptomics data provides new insights into the molecular mechanisms of LUSC and may be helpful in identifying biomolecular markers for early disease diagnosis.