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A Systematic Approach Introduced Some Immune System Targets in Rectal Cancer by Considering Cell-Free Dna Methylation in Response to Radiochemotherapy Publisher Pubmed



Bagherihosseinabadi Z1, 2 ; Eshkevari SMS2 ; Khalighfard S3 ; Alizadeh AM4, 5 ; Khori V6 ; Amiriani T6 ; Poorkhani A6 ; Sadani S6 ; Esmati E4 ; Lashgari M4 ; Mahmoodi M1, 7 ; Hajizadeh MR1, 2
Authors
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Authors Affiliations
  1. 1. Molecular Medicine Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
  2. 2. Department of Clinical Biochemistry, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran
  3. 3. Research Center for Development of Advanced Technologies, Tehran, Iran
  4. 4. Radiation Oncology Research Center, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Cancer Research Center, Cancer Institute, Tehran University of Medical Sciences, Tehran, Iran
  6. 6. Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran
  7. 7. Department of Clinical Biochemistry, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran

Source: Cytokine Published:2024


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. © 2024 Elsevier Ltd
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