Tumor Microenvironment in Clear Cell Renal Cell Carcinoma: A Comprehensive Analysis.

IF 1.4 4区 医学 Q3 Medicine Iranian Journal of Public Health Pub Date : 2024-11-01 DOI:10.18502/ijph.v53i11.16957
Zhuangyu Guo, Xue Wang, Shuaishuai Huang, Guobin Weng
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Abstract

Background: M6A RNA methylation and the tumor microenvironment (TME) have been reported to play important roles in the progression and prognosis of clear cell renal cell carcinoma (ccRCC). However, whether m6A RNA methylation regulators affect the TME in ccRCC remains unknown. Thus, we aimed to evaluate comprehensively the effect of m6A RNA methylation regulators on the TME in ccRCC.

Methods: Transcriptome data of ccRCC were obtained from TCGA database. Consensus clustering analysis was conducted based on the expression of m6A RNA methylation regulators. Survival differences were evaluated by Kaplan-Meier analysis between the clusters. The DESeq2 package was used to analyze the differentially expressed genes (DEGs) between the clusters. GO and KEGG pathway analyses were performed by the ClusterProfiler R package. The CIBERSORT algorithm was used to evaluate immune infiltration.

Results: The expression of 15 m6A regulators significantly differed between ccRCC and normal kidney tissues. Based on the expression of these 15 m6A regulators, two clusters were identified by consensus clustering, in which cluster 1 had better overall survival (OS). Overall, 4,429 DEGs were identified between the two clusters and were enriched in immune-related biological processes. Cluster 1 had lower immune and ESTIMATE scores, higher expression of HLA and lower expression of immune checkpoint molecules. Moreover, immune infiltration and expressions of Th1/IFNγ gene signature were also significantly different between the two clusters.

Conclusion: Our study revealed m6A regulators were important participants in the development of ccRCC, with a close relationship with the TME.

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透明细胞肾细胞癌肿瘤微环境的综合分析。
背景:M6A RNA甲基化和肿瘤微环境(tumor microenvironment, TME)在透明细胞肾细胞癌(clear cell renal cell carcinoma, ccRCC)的进展和预后中起重要作用。然而,m6A RNA甲基化调节因子是否影响ccRCC中的TME仍然未知。因此,我们旨在全面评估m6A RNA甲基化调节剂对ccRCC中TME的影响。方法:从TCGA数据库中获取ccRCC的转录组数据。基于m6A RNA甲基化调控因子的表达进行共识聚类分析。通过Kaplan-Meier分析评估各组间的生存差异。使用DESeq2软件包分析集群之间的差异表达基因(DEGs)。GO和KEGG通路分析由ClusterProfiler R包执行。采用CIBERSORT算法评价免疫浸润。结果:15个m6A调节因子在ccRCC和正常肾组织中的表达有显著差异。基于这15个m6A调节因子的表达,通过共识聚类确定了两个簇,其中簇1具有更好的总生存(OS)。总体而言,在两个集群之间鉴定出4,429个deg,并且在免疫相关的生物过程中富集。簇1免疫和ESTIMATE评分较低,HLA表达较高,免疫检查点分子表达较低。此外,免疫浸润和Th1/IFNγ基因标记的表达在两个集群之间也有显著差异。结论:我们的研究表明m6A调节因子是ccRCC发展的重要参与者,与TME密切相关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Iranian Journal of Public Health
Iranian Journal of Public Health 医学-公共卫生、环境卫生与职业卫生
CiteScore
2.20
自引率
7.10%
发文量
0
审稿时长
2 months
期刊介绍: Iranian Journal of Public Health has been continuously published since 1971, as the only Journal in all health domains, with wide distribution (including WHO in Geneva and Cairo) in two languages (English and Persian). From 2001 issue, the Journal is published only in English language. During the last 41 years more than 2000 scientific research papers, results of health activities, surveys and services, have been published in this Journal. To meet the increasing demand of respected researchers, as of January 2012, the Journal is published monthly. I wish this will assist to promote the level of global knowledge. The main topics that the Journal would welcome are: Bioethics, Disaster and Health, Entomology, Epidemiology, Health and Environment, Health Economics, Health Services, Immunology, Medical Genetics, Mental Health, Microbiology, Nutrition and Food Safety, Occupational Health, Oral Health. We would be very delighted to receive your Original papers, Review Articles, Short communications, Case reports and Scientific Letters to the Editor on the above men­tioned research areas.
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