| 摘要: |
| 目的 应用生物信息学技术分析筛选影响宫颈癌预后的关键基因并深度挖掘基因功能。方法 从基因表达汇编（GEO）数据库下载宫颈癌微阵列数据集（GSE6791、GSE39001、GSE55940、GSE63678），合并和批量标准化后筛选差异表达基因（DEG）。对DEG进行基因本体（GO）和京都基因和基因组百科全书（KEGG）通路富集分析及蛋白质-蛋白质相互作用（PPI）网络构建，利用癌症基因组图谱（TCGA）数据库进行生存分析以确定关键基因。对关键基因进行基因功能集富集分析，并且利用基于TCGA数据库的泛癌数据进行深度的功能挖掘，包括基因相关性分析、单因素Cox回归、免疫亚型、肿瘤微环境和肿瘤干性分析。结果 共筛选出336个DEG，其中153个下调、183个上调。PPI网络和生存分析结果显示微小染色体维持蛋白（MCM）2是宫颈癌的潜在生物标志物。基因功能集富集分析提示，MCM2与自噬和MAPK信号通路有关。在泛癌数据中的研究表明，MCM2的表达水平与4种恶性肿瘤（宫颈癌、弥漫大B细胞淋巴瘤、直肠腺癌、葡萄膜黑素瘤）的5年总生存率呈正相关，与7种恶性肿瘤（肾上腺皮质癌、肾嫌色细胞癌、急性髓细胞样白血病、脑低级别胶质瘤、肝细胞肝癌、间皮瘤、肉瘤）的5年总生存率呈负相关（P均<0.05）。深度功能挖掘提示，MCM2~10参与肿瘤组织免疫亚型的改变，高表达MCM2~10的肿瘤组织中可能存在较低比例的基质细胞和免疫细胞及较高比例的肿瘤细胞；在多种肿瘤中，MCM2的表达水平与肿瘤细胞的干性特征呈正相关。结论 MCM2在宫颈癌中高表达且与患者预后相关，是宫颈癌的潜在预后标志物。在多种恶性肿瘤中，MCM2参与多种生物过程，可能成为恶性肿瘤治疗干预的新靶点。 |
| 关键词: 宫颈肿瘤 MCM2 生物信息学 泛癌 肿瘤微环境 肿瘤干细胞 |
| DOI：10.16781/j.0258-879x.2021.04.0399 |
| 投稿时间：2020-12-09修订日期：2021-02-03 |
| 基金项目:国家重点研发计划重大慢性非传染性疾病防控研究重点专项（2016YFC1303101），海军军医大学（第二军医大学）长海医院"234学科攀峰计划"（2019YXK014）. |
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| Screening and verifying biomarker mini-chromosome maintenance protein 2 for cervical cancer based on bioinformatics |
| JIANG Wei-qi△,WANG Jing△,HE Hai-wei,CHEN Jun,LIU Chen-wu,XU Ming-juan* |
(Department of Obstetrics and Gynaecology, Changhai Hospital, Naval Medical University(Second Military Medical University), Shanghai 200433, China
△Co-first authors.
* Corresponding author) |
| Abstract: |
| Objective To analyze and screen key genes affecting the prognosis of cervical cancer based on bioinformatics, and to explore their functions. Methods The microarray datasets of cervical cancer (GSE6791, GSE39001, GSE55940 and GSE63678) were downloaded from Gene Expression Omnibus (GEO) database, and the differentially expressed genes (DEGs) were screened after merging and batch normalization. The DEGs were analyzed by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses and protein-protein interaction (PPI) network, and survival analysis was performed based on The Cancer Genome Atras (TCGA) database to identify key genes. The functions of key genes were analyzed by gene set enrichment analysis (GSEA), and the pan-cancer data based on TCGA database were used for in-depth research on functions, including gene correlation analysis, univariate Cox regression, immune subtype, tumor microenvironment and tumor stemness. Results A total of 336 DEGs were screened out, of which 153 were down-regulated and 183 were up-regulated. Mini-chromosome maintenance protein 2 (MCM2) was selected as a potential biomarker for cervical cancer by PPI network and survival analysis. The results of GSEA suggested that MCM2 was associated with autophagy and mitogen-activated protein kinase signaling pathway. The research in pan-cancer showed that the expression of MCM2 was positively correlated with the 5-year overall survival rates of 4 cancers (cervical cancer, lymphoid neoplasm diffuse large B-cell lymphoma, rectum adenocarcinoma, and uveal melanoma) and negatively correlated with 7 cancers (adrenocortical carcinoma, kidney chromophobe, acute myeloid carcinoma, brain lower grade glioma, liver hepatocellular carcinoma, mesothelioma and sarcoma). The research on functions in pan-cancer data suggested that MCM2-10 were invoved in the immune subtypes of cancers; tumor tissues with high expression levels of MCM2-10 had low proportions of matrix cells and immune cells and a high proportion of cancer cells; and the expression level of MCM2 was positively correlated with the tumor stemness in many cancers. Conclusion MCM2 is highly expressed in cervical cancer and related to the prognosis of patients, making it a potential biomarker for prognosis of cervical cancer. Furthermore, MCM2 is involved in various biological processes of many cancers, and it serves as a new target for cancer therapeutic intervention. |
| Key words: uterine cervical neoplasms mini-chromosome maintenance protein 2 bioinformatics pan-cancer tumor microenvironment neoplastic stem cells |
