Methylation of Sept9 and Linc00473 Genes in Circulating Cell-Free Dna As a Potential Biomarker for the Early Detection of Colorectal Polyps Publisher

Summary: Study shows SEPT9 and LINC00473 methylation could non-invasively detect polyps. Are we closer to early CRC diagnosis? #CancerResearch #EarlyDetection

Tat M ; Heiat M ; Karbasi A ; Abyazi MA ; Zakidizaji M
Source: Advanced Biomedical Research Published:2025

Abstract

Background: Recently, there has been a growing amount of data suggesting the significance of long noncoding RNAs (lncRNAs) in controlling cellular biological processes and influencing the progression of cancer. Changes in the methylation of promoter regions in these lncRNA genes can interfere with their expression and functions. The aim of this study was to evaluate the methylation status of SEPT9 and LINC00473 genes in plasma for the non-invasive early detection of polyps. Materials and Methods: In this study, 27 individuals with low-risk polyps (LRP), 27 with high-risk polyps (HRP), and 26 healthy controls were enrolled. The quantitative methylation levels of specific sites in SEPT9 and LINC00473 genes were examined in cell-free DNA (cfDNA) extracted from the plasma of all participants using a methylation-quantification endonuclease-resistant DNA (MethyQESD) method. Results: Increased methylation percentages of both SEPT9 and LINC00473 (LINC00473-1 and LINC00473-2) were observed in individuals with LRP and HRP. The combination of SEPT9 and LINC00473-2 improved the diagnostic power and significance (AUC = 0.822; 95% CI: 0.696 to 0.912, P < 0.001) with sensitivity of 69% (95% CI: 49-85%) and specificity of 96% (95 CI: 80-99%) for LRP. A combination of SEPT9 and LINC00473-1 showed an AUC of 0.925 (95% CI: 0.826 to 0.978, P < 0.001) with a sensitivity of 88% (95% CI: 72-97%) and specificity of 96% (95 CI: 80-99%) for HRP. Conclusions: LINC00473 can enhance the specificity of SEPT9 methylation-specific detection of precancerous lesions. The combined detection of SEPT9 and LINC00473 offers a simple and accurate screening tool for polyp detection, showing promise for the early non-invasive detection of CRC and associated precancerous lesions. © 2025 Elsevier B.V., All rights reserved.