A systematic approach introduced some immune system targets in rectal cancer by considering cell-free DNA methylation in response to radiochemotherapy

IF 3.7 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Zahra Bagheri-Hosseinabadi , Seyed Mohammad Sadat Eshkevari , Solmaz Khalighfard , Ali Mohammad Alizadeh , Vahid Khori , Taghi Amiriani , Amirhoushang Poorkhani , Somayeh Sadani , Ebrahim Esmati , Marzih Lashgari , Mehdi Mahmoodi , Mohammad Reza Hajizadeh
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引用次数: 0

Abstract

Background

This study aims to investigate cell-free DNA (cfDNA) methylation of genes involved in some immune system targets as biomarkers of radioresistance in patients with non-metastatic rectal cancer.

Methods

Gene expression (GSE68204, GPL6480, and GSE15781) and DNA methylation profiles (GSE75548 and GSE139404) of rectal cancer patients were obtained from the Gene Expression Omnibus (GEO) database. GEO2R and FunRich software were first used to identify genes with significant expression differences. Enricher softwer was then used to analyze Gene Ontology and detect pathway enrichment of hub genes. Blood samples were then taken from 43 rectal cancer patients. After cfDNA extraction from samples, it was treated with bisulfite and analyzed by methylation-specific PCR.

Results

1088 genes with high and 629 with low expression were identified by GEO2R and FunRich software. A total of five high-expression hub genes, including CDH24, FGF18, CCND1, IFITM1, UBE2V1, and three low-expression hub genes, including CBLN2, VIPR2, and IRF4, were identified from UALCAN and DNMIVD databases. Methylation-specific PCR indicated a significant difference in hub gene methylation between cancerous and non-cancerous individuals. Radiochemotherapy significantly affected hub gene methylation. There was a considerable difference in the methylation rate of hub genes between patients who responded to radiochemotherapy and those who did not.

Conclusions

Evaluating gene methylation patterns might be an appropriate diagnostic tool to predict radiochemotherapy response and develop targeted therapeutic agents.

通过考虑放化疗反应中的无细胞 DNA 甲基化,系统性地介绍直肠癌中的一些免疫系统靶点
方法从基因表达总库(GEO)数据库中获取直肠癌患者的基因表达(GSE68204、GPL6480和GSE15781)和DNA甲基化图谱(GSE75548和GSE139404)。首先使用 GEO2R 和 FunRich 软件识别具有显著表达差异的基因。然后使用 Enricher 软件分析基因本体,检测枢纽基因的通路富集。然后采集了 43 名直肠癌患者的血样。结果 GEO2R 和 FunRich 软件识别出 1088 个高表达基因和 629 个低表达基因。从 UALCAN 和 DNMIVD 数据库中共鉴定出 CDH24、FGF18、CCND1、IFITM1、UBE2V1 等 5 个高表达中心基因和 CBLN2、VIPR2、IRF4 等 3 个低表达中心基因。甲基化特异性聚合酶链反应(PCR)结果显示,癌症患者和非癌症患者的中枢基因甲基化存在显著差异。放化疗对中枢基因甲基化有明显影响。结论评估基因甲基化模式可能是预测放化疗反应和开发靶向治疗药物的适当诊断工具。
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
Cytokine
Cytokine 医学-免疫学
CiteScore
7.60
自引率
2.60%
发文量
262
审稿时长
48 days
期刊介绍: The journal Cytokine has an open access mirror journal Cytokine: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. * Devoted exclusively to the study of the molecular biology, genetics, biochemistry, immunology, genome-wide association studies, pathobiology, diagnostic and clinical applications of all known interleukins, hematopoietic factors, growth factors, cytotoxins, interferons, new cytokines, and chemokines, Cytokine provides comprehensive coverage of cytokines and their mechanisms of actions, 12 times a year by publishing original high quality refereed scientific papers from prominent investigators in both the academic and industrial sectors. We will publish 3 major types of manuscripts: 1) Original manuscripts describing research results. 2) Basic and clinical reviews describing cytokine actions and regulation. 3) Short commentaries/perspectives on recently published aspects of cytokines, pathogenesis and clinical results.
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