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RNA甲基化修饰相关基因在结直肠癌预后及免疫治疗中的作用

The Role of RNA Methylation Modification Related Genes in Prognosis and Immunotherapy of Colorectal Cancer.

作者信息

Lin Ruoyang, Chen Renpin, Ye Lechi, Huang Zhiming, Lin Xianfan, Chen Tanzhou

机构信息

Department of Gastroenterology and Hepatology, the First Affiliated Hospital of Wenzhou, Medical University, Wenzhou, People's Republic of China.

Department of Colorectal and Anal Surgery, the First Affiliated Hospital of Wenzhou, Medical University, Wenzhou, People's Republic of China.

出版信息

Int J Gen Med. 2023 May 31;16:2133-2147. doi: 10.2147/IJGM.S405419. eCollection 2023.

Abstract

BACKGROUND

Researches showed RNA methylation genes can affect the prognosis of tumors. Thus, the study aimed to comprehensively analyze the effects of RNA methylation regulatory genes in prognosis and treatment of colorectal cancer (CRC).

METHODS

Prognostic signature associated with CRCs were constructed by differential expression analysis, Cox and Least Absolute Shrinkage and Selection Operator (LASSO) analyses. Receiver operating characteristic (ROC) and Kaplan-Meier survival analyses were used to validate the reliability of the developed model. Gene Ontology (GO), Gene set variation analysis (GSVA), and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed for functional annotation. Finally, normal and cancerous tissue were collected to validate gene by quantitative real-time PCR (qRT-PCR).

RESULTS

A prognostic risk model based on leucine rich pentatricopeptide repeat containing (LRPPRC) and ubiquitin-like with PHD and ring finger domains 2 (UHRF2) was constructed and relevant to the overall survival (OS) of CRC. Functional enrichment analysis revealed that collagen fibrous tissue, ion channel complex and other pathways were significantly enriched, which might help explain the underlying molecular mechanisms. There were significant differences in ImmuneScore, StromalScore, ESTIMATEScore between high- and low-risk groups (p < 0.05). Ultimately, qRT-PCR validation showed that a significant upregulation in the expression of LRPPRC and UHRF2 in cancerous tissue, which verified the effectiveness of our signature.

CONCLUSION

In conclusion, 2 prognostic genes (LRPPRC and UHRF2) related to RNA methylation were identified by bioinformatics analysis, which might supply a new insight into the treatment and evaluation of CRC.

摘要

背景

研究表明RNA甲基化基因可影响肿瘤预后。因此,本研究旨在全面分析RNA甲基化调控基因在结直肠癌(CRC)预后及治疗中的作用。

方法

通过差异表达分析、Cox分析和最小绝对收缩与选择算子(LASSO)分析构建与结直肠癌相关的预后特征。采用受试者工作特征(ROC)和Kaplan-Meier生存分析来验证所建立模型的可靠性。进行基因本体论(GO)、基因集变异分析(GSVA)和京都基因与基因组百科全书(KEGG)通路分析以进行功能注释。最后,收集正常组织和癌组织通过定量实时PCR(qRT-PCR)验证基因。

结果

构建了基于富含亮氨酸的五肽重复序列蛋白(LRPPRC)和含PHD及环指结构域的泛素样蛋白2(UHRF2)的预后风险模型,该模型与结直肠癌的总生存期(OS)相关。功能富集分析显示胶原纤维组织、离子通道复合物等通路显著富集,这可能有助于解释潜在的分子机制。高风险组和低风险组之间的免疫评分、基质评分、估计评分存在显著差异(p<0.05)。最终,qRT-PCR验证显示癌组织中LRPPRC和UHRF2的表达显著上调,这验证了我们所构建特征的有效性。

结论

总之,通过生物信息学分析鉴定出2个与RNA甲基化相关的预后基因(LRPPRC和UHRF2),这可能为结直肠癌的治疗和评估提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01b5/10239628/257e3ddedbfd/IJGM-16-2133-g0001.jpg

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