DOI: 10.4103/abr.abr_481_25 ISSN: 2277-9175

IGF2 DMR0 Hypomethylation in Peripheral Blood Mononuclear Cells: A Noninvasive Prognostic Biomarker for Colorectal Cancer

Elham Zare, Mozhdeh Saghaei, Meysam Mosallaei, Hassan Mehrad-Majd, Ali Beheshti Namdar
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Abstract

Background:

Conventional colorectal cancer (CRC) screening methods are hindered by invasiveness and insufficient accuracy, emphasizing the need for noninvasive biomarkers. DNA methylation alterations occur early in tumor development, and hypomethylation of the IGF2 DMR0 region disrupts normal imprinting, leading to IGF2 overexpression and subsequent tumor progression. Given that peripheral blood mononuclear cells (PBMCs) not only provide an indirect source of biomarkers but also mirror the methylation profile of tumor cells, we evaluated IGF2 DMR0 methylation in PBMCs from Iranian CRC patients and healthy controls.

Materials and Methods:

PBMCs were isolated from peripheral blood specimens obtained from 62 sporadic CRC participants and 62 healthy individuals. The quantitative methylation analysis of the IGF2 DMR0 region was conducted using the methylation quantification endonuclease-resistant DNA (MethyQESD) method.

Results:

The methylation level of IGF2 DMR0 was found to be lower in CRC patients (21.44 ± 16.77%) compared to controls (24.63 ± 16.27%); however, this observed disparity did not reach statistical significance ( P : 0.286). When stratified by tumor stage, early-stage tumors (Stages I and II) showed significantly higher methylation levels than advanced-stage tumors (Stages III and IV) ( P < 0.001). Furthermore, Pearson correlation analysis discovered a significant negative association between tumor size and methylation level (r: -0.624, P < 0.001). No remarkable correlations were identified between methylation levels and other parameters such as gender, age, tumor location, or smoking status ( P > 0.05).

Conclusion:

Our findings proposed that hypomethylation of the IGF2 DMR0 region is meaningfully linked with tumor progression and growth, underscoring its potential as a noninvasive prognostic biomarker for CRC.

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