[1]邵 波,汪 进a,万 水a,等.基于生物信息学构建膀胱尿路上皮癌的ceRNA网络以及关键mRNA与免疫功能分析[J].现代检验医学杂志,2024,39(01):29-35+66.[doi:10.3969/j.issn.1671-7414.2024.01.006]
　SHAO Bo,WANG Jina,WAN Shuia,et al.Construction of ceRNA Network and Analysis of Key mRNA and Immune Function for Bladder Urothelial Carcinoma Based on Bioinformatics[J].Journal of Modern Laboratory Medicine,2024,39(01):29-35+66.[doi:10.3969/j.issn.1671-7414.2024.01.006]
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基于生物信息学构建膀胱尿路上皮癌的ceRNA网络以及关键mRNA与免疫功能分析()
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《现代检验医学杂志》[ISSN:/CN:]

卷:
第39卷
期数:
2024年01期
页码:
29-35+66
栏目:
论著
出版日期:
2024-01-15

文章信息/Info

Title:
Construction of ceRNA Network and Analysis of Key mRNA and Immune Function for Bladder Urothelial Carcinoma Based on Bioinformatics
文章编号:
1671-7414（2024）01-029-08
作者:
邵 波1; 汪 进2a; 万 水2a; 吴开秀3; 田 申2a; 杜沂宸2b; 陈丹霞2b; 马园园2c
（1. 安徽中医药大学附属芜湖市中医医院专业学位硕士研究生培养基地，安徽芜湖 241003；2. 安徽中医药高等专科学校附属医院/ 芜湖市中医医院a. 泌尿外科；b. 皮肤科；c. 肛肠科，安徽芜湖 241001；3. 昆明医科大学海源学院，昆明 650106）
Author(s):
SHAO Bo1;  WANG Jin2a;  WAN Shui2a;  WU Kaixiu3;  TIAN Shen2a;  DU Yichen2b;  CHEN Danxia2b;  MA Yuanyuan2c
（1. Wuhu Hospital of Traditional Chinese Medicine Affiliated to Anhui University of Traditional Chinese Medicine Professional Degree Postgraduate Training Base, Anhui Wuhu 241003, China；2a.Department of Urology; 2b.Department of Dermatology; 2c.Department of Proctology, Affiliated Hospital of Anhui College of Traditional Chinese Medicine / Wuhu Hospital of Traditional Chinese Medicine, Anhui Wuhu 241001, China；3. Kunming Medical University Haiyuan College, Kunming 650106, China）
关键词:
膀胱尿路上皮癌; 信使核糖核酸; 内源竞争性RNA; 免疫功能
分类号:
R737.14；R730.43
DOI:
10.3969/j.issn.1671-7414.2024.01.006
文献标志码:
A
摘要:
目的　构建膀胱尿路上皮癌（bladder urothelial carcinoma，BLCA）具有预后价值的内源竞争性核糖核酸（competing endogenous RNA，ceRNA）调控网络，分析关键信使RNA（messenger RNA，mRNA）与免疫功能的关系。方法　UCSC Xena 数据库下载404 例BLCA 患者和28 例正常人的mRNA 表达数据，通过差异分析筛选关键mRNA。ENCORI 数据库中查找与关键mRNA 结合的微小核糖核酸（micro RNA，miRNA）以及与miRNA 结合的长链非编码核糖核酸（long non-coding RNA，LncRNA）。TCGA 数据库下载miRNA 和LncRNA 的表达数据，对关键mRNA 与所有miRNA 以及miRNA 与所有LncRNA 进行共表达分析，筛选出关键的miRNA 和LncRNA。根据关键mRNA，miRNA和LncRNA 在肿瘤患者和正常人之间表达量的差异进行生存分析，最后构建了ceRNA 调控网络。借助TIMER 2.0 数据库，分析关键mRNA 与免疫细胞、免疫检查点（CD274，PDCD1，CTLA4）以及免疫细胞标记基因（immunomarkergenes，IG）的相关性。结果　筛选出关键mRNA* 共22 个，其中差异显著性最高的是脯氨酸3- 羟化酶4（proline3-hydroxylase 4，P3H4）。在BLCA 中，P3H4 表达高，在高表达组患者的生存时间较短。以关键mRNA 为中心环节，共筛选出33 个miRNA 和14 个LncRNA。经过共表达分析和生存分析后，筛选出具有预后价值的关键miRNA 和关键LncRNA 分别为hsa-miR-151a-3p 和MIR100HG。上述分析结果差异具有统计学意义（均Ρ ＜ 0.05）。综合以上结果，构建了包含1 个mRNA，1 个miRNA 和1 个LncRNA 的ceRNA 调控网络。免疫分析首次在BLCA 肿瘤微环境中发现了与P3H4 表达量呈显著正相关的双阳性T 细胞。此外还有3 种免疫细胞（肿瘤相关性中性粒细胞、肿瘤相关巨噬细胞、树突状细胞）、3 个免疫检查点（CD274，PDCD1，CTLA4）以及15 个IG 与P3H4 相关度显著，这些差异具有统计学意义（均Ρ ＜ 0.01）。结论　该研究有助于揭示BLCA 的进展机制，构建的ceRNA 网络及免疫分析，可为BLCA 患者的诊断、治疗、预测提供新的生物学靶点和方向。
Abstract:
Objective　To construct a regulatory network of competing endogenous RNA (ceRNA) with prognostic value for bladder urothelial carcinoma (BLCA), and analyze the relationship between key messenger RNA (mRNA) and immune function. Methods　The UCSC Xena database was used to download mRNA expression data from 404 BLCA patients and 28 normal individuals and key mRNAs were screened by differential analysis. ENCORI database was utilized to search microRNAs (miRNAs) that bind to key mRNAs and all long non-coding RNAs (LncRNAs) that bind to miRNAs. The expression data of miRNA and LncRNA were downloaded from TCGA database, co-expression analysis was performed to identify key mRNA with all miRNAs and miRNA with all LncRNAs, and thus key miRNAs and LncRNAs were screened out. Survival analysis was conducted based on the differences in expression levels of these key mRNAs, miRNAs, and LncRNAs between tumor patients and normal individuals, and finally a ceRNA regulatory network was constructed. The correlation between key mRNAs and immune cells, immune checkpoints (CD274, PDCD1 and CTLA4), and immune cell marker genes (IG) was analyzed using the TIMER 2.0 database. Results　A total of 22 key mRNAs were screened, with the most significant difference being proline 3-hydroxylase 4 (P3H4). The expression of P3H4 in patients with BLCA was high, and survival time was shorter in patients with high expression. A sum of 33 miRNAs and 14 LncRNAs were screened using the key mRNAs as the central link. Through coexpression analysis and survival analysis, hsa-miR-151a-3p and MIR100 HG were identified as the key miRNA and key LncRNA with prognostic value. The differences in the above analysis results were statistically significant (all Ρ < 0.05). Based on these findings, a ceRNA regulatory network consisting of 1 mRNA, 1 miRNA, and 1 LncRNA was constructed. Immunoassay firstly revealed a significant positive correlation between double positive T cells and P3H4 expression in the tumor microenvironment of BLCA. Moreover, there were 3 types of immune cells (tumor-associated neutrophils, and tumor-associated macrophages, dendritic cells), 3 immune checkpoints (CD274, PDCD1, CTLA4), and 15 IGs with significant correlation with P3H4. These differences were statistically significant (all Ρ< 0.01). Conclusion　This study could help to reveal the progression mechanism of BLCA. The constructed ceRNA network and immune analysis can offer new insights into potential biological targets and immunotherapy directions for the diagnosis, treatment, and prediction of BLCA patients.

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备注/Memo

备注/Memo:
基金项目： 安徽省高等学校科学研究项目（2022AH052642）：个体化预测上尿路结石术后留置双J 管致严重LUTS 的风险Nomogram 模型的构建与验证；芜湖市科技成果转化项目（2021cg07）：芜湖市5G+ 中医治未病健康管理服务云平台的构建与示范研究；芜湖市科技成果转化项目（2022cg37）：一期输尿管软镜碎石术临床应用及影响因素分析。
作者简介：邵波(1997-)，男，硕士，住院医师，研究方向：中医药防治泌尿生殖外科疾病研究，E-mail：zywkxsb@126.com。
通讯作者：万水(1977-)，男，硕士，主任医师，研究方向：泌尿生殖外科学，E-mail： 18855300839@139.com。
更新日期/Last Update: 2024-01-15