通讯作者: 于琦, yuqi@sxmu.edu.cn

DOI：10.12201/bmr.202303.00017

Protein-based bioinformatics analysis of cervical cancer-related genes

• 摘要：目的/意义本研究旨在通过生物信息学挖掘与宫颈癌(CESC)相关的基因,探讨了与HPVE6E7密切相关差异表达基因（DEGs）的表达特征及临床意义。方法/过程从UCSC获取TCGA和GTEx中CESC的宫颈组织及临床信息，作为训练集。从GEO中获取与CESC相关的表达谱芯片GSE63514作为验证集。使用R软件limma包筛选肿瘤和正常样本的DEGs，制作与MigDB数据库中E6E7蛋白相关基因的Venn图。通过survival包进行批量生存分析,并通过ROC和蛋白表达水平进行验证。其次，通过拷贝数变异和甲基化相关性得到关键基因。最后，构建特异性共表达网络并进行富集分析和免疫浸润分析。结果/结论与HPVE6E7蛋白相关的DEGs有101个,生存分析和ROC分析共筛选出8个关键DEGs。经蛋白水平进行验证后发现有4个基因与mRNA水平表达情况一致分别是CHAF1B?E2F1?MCM4和PCNA。经过拷贝数和甲基化相关性分析后，筛选出3个基因有显著意义，分别是E2F1?MCM4和PCNA。同时,经通路分析后发现特异性共表达网络中的基因显著富集在DNA复制?染色体组织?核染色体等通路。最后，通过免疫相关性分析发现关键基因与CD4 T细胞，B细胞和中性粒细胞显著相关。E2F1、MCM4、PCNA、DNA复制，染色体组织等为CESC发生发展以及HPVE6E7编码蛋白显著相关的分子机制和关键基因。

  关键词： 宫颈癌; 宫颈组织; 差异基因; HPVE6E7编码蛋白

   

  Abstract: The aim of this study was to explore the expression characteristics and clinical significance of differentially expressed genes (DEGs) closely related to HPVE6E7 through bioinformatics mining of genes associated with cervical cancer (CESC). Method The cervical tissue and clinical information of CESC in TCGA and GTEx were obtained from UCSC as the training set. The expression profile chip GSE63514 associated with CESC from GEO was obtained as the validation set. The DEGs of tumor and normal samples were screened using the R software limma package to produce Venn diagrams of genes associated with the E6E7 protein in the MigDB database. Bulk survival analysis was performed by survival package and validated by ROC and protein expression levels. Next, key genes were obtained by copy number variation and methylation correlation. Finally, specific co-expression networks were constructed and subjected to enrichment analysis and immuno-infiltration analysis. ResultsThere were 101 DEGs associated with HPVE6E7, and 8 DEGs were screened after survival and ROC analysis. After verification at the protein level, four genes were found to be consistent with expression at the mRNA level, namely CHAF1B, E2F1, MCM4, and PCNA. Through copy number and methylation correlation analysis, three genes were selected as significant, respectively, E2F1, MCM4, and PCNA. Meanwhile, the genes in the specific co-expression network were strongly enriched in DNA replication, chromosome organization, nuclear chromosomes, etc. Eventually, immune correlation analysis revealed significant correlations with CD4 T cells, B cells, and neutrophils.E2F1, MCM4, PCNA, DNA replication, chromosome organization, etc., were the molecular mechanisms and key pivot genes for the occurrence and development of CESC and the protein encoded by HPVE6E7.

  Key words: Cervical cancer; cervical tissue; Differentially Expressed Genes; HPVE6E7 encoded protein

  提交时间：2023-03-22

  版权声明：作者本人独立拥有该论文的版权，预印本系统仅拥有论文的永久保存权利。任何人未经允许不得重复使用。
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• 序号	提交日期	编号	操作
  1	2023-01-31	bmr.202303.00017V1	下载

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