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Published on: April 22, 2019
A systematic approach introduced some immune system targets in rectal cancer by considering cell-free DNA methylation
Zahra Bagheri-Hosseinabadi1, Seyed Mohammad Sadat Eshkevari2, Solmaz Khalighfard3
1Molecular Medicine Research Center, Research Institute of Basic Medical Sciences, Rafsanjan University of Medical Sciences, Rafsanjan, Iran; Department of Clinical Biochemistry, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
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.
Insights
Cell-free DNA methylation patterns in rectal cancer patients can predict response to radiochemotherapy. This finding may aid in developing targeted therapies and improving patient outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Investigating cell-free DNA (cfDNA) methylation of immune targets.
- Identifying biomarkers for radioresistance in non-metastatic rectal cancer.
Purpose of the Study:
- To explore cfDNA methylation patterns as predictors of radiochemotherapy response.
- To assess the diagnostic potential of gene methylation for rectal cancer treatment.
Main Methods:
- Utilized Gene Expression Omnibus (GEO) data for gene expression and methylation profiles.
- Employed GEO2R, FunRich, and Enricher software for gene identification and pathway analysis.
- Performed methylation-specific PCR on cfDNA from 43 rectal cancer patients.
Main Results:
- Identified significant differences in hub gene methylation between cancerous and non-cancerous samples.
- Confirmed that radiochemotherapy significantly impacts hub gene methylation.
- Observed distinct methylation rates correlating with patient response to radiochemotherapy.
Conclusions:
- Gene methylation patterns serve as potential diagnostic tools.
- Methylation analysis can predict radiochemotherapy response in rectal cancer.
- This approach may facilitate the development of targeted therapeutic agents.
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