Differential methylation of DNA promoter sequences in peripheral blood mononuclear cells as promising diagnostic biomarkers for colorectal cancer

Meysam Mosallaei ¹, Goli Siri ², Behrang Alani ³

⁰Department of Genetics and Advanced Medical Technology, Faculty of Medicine, AJA University of Medical Sciences, Tehran, Iran.

Journal of Cancer Research and Therapeutics +

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July 18, 2024

View abstract on PubMed

Summary

Promoter methylation of the RUNX3 gene in peripheral blood mononuclear cells (PBMCs) shows promise for early colorectal cancer (CRC) detection. This non-invasive method offers high accuracy in distinguishing CRC patients from healthy individuals.

Area Of Science

Oncology
Molecular Biology
Genetics

Background

Colorectal cancer (CRC) presents a high mortality rate, often due to late diagnosis.
Early detection through screening significantly reduces CRC-related deaths.
Aberrant gene methylation in peripheral blood mononuclear cells (PBMCs) is linked to CRC.

Purpose Of The Study

To investigate the potential of quantitative promoter methylation analysis of RUNX3 and RASSF1A genes in PBMCs for early, non-invasive CRC diagnosis.
To establish RUNX3 and RASSF1A methylation as biomarkers for colorectal cancer screening.

Main Methods

Analysis of RUNX3 and RASSF1A promoter methylation status in 70 CRC patients and 70 healthy controls.
Utilized methylation-quantification of endonuclease-resistant DNA (MethyQESD), a bisulfite conversion-independent method.
Assessed diagnostic accuracy using sensitivity, specificity, and receiver operating characteristic (ROC) curve analysis.

Main Results

RUNX3 was significantly hypermethylated in PBMCs of CRC patients compared to controls (P < 0.001).
RUNX3 promoter methylation demonstrated high diagnostic accuracy (AUC = 0.840) with 84.28% sensitivity and 77.14% specificity.
RUNX3 methylation levels correlated with CRC disease stage (P < 0.001), while RASSF1A showed no significant differences.

Conclusions

PBMCs are a reliable source for methylation analysis in CRC screening.
RUNX3 promoter methylation serves as a promising biomarker for the early diagnosis of colorectal cancer.