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Article type: Research Article
Authors: Alizadeh-Sedigh, Maryama | Fazeli, Mohammad Sadeghb | Mahmoodzadeh, Habibollahc | Sharif, Shahin Behrouza | Teimoori-Toolabi, Ladana; *
Affiliations: [a] Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran | [b] Department of Surgery, Division of Colorectal Surgery, Imam Khomeini Medical Complex, Tehran University of Medical Sciences, Tehran, Iran | [c] Cancer Institute of Iran, Imam Khomeini Medical Complex, Tehran University of Medical Sciences, Tehran, Iran
Correspondence: [*] Corresponding author: Ladan Teimoori-Toolabi, Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, 69 th Pasteur Avenue, Kargar Street, Tehran, Iran. P.O Box: 1316943551; Tel.: +98 21 6411 2455; Fax: +98 21 66480780; %****␣cbm-34-cbm210315_temp.tex␣Line␣50␣**** E-mail: lteimoori@pasteur.ac.ir.
Abstract: BACKGROUND: Investigating aberrant tumor-specific methylation in plasma cell-free DNA provides a promising and noninvasive biomarker for cancer detection. OBJECTIVE: We aimed to investigate methylation status of some promoter regions in the plasma and tumor tissues to find biomarkers for early detection of colorectal cancer. METHODS: This case-control study on seventy colorectal cancer patients and fifty matched healthy controls used Methylation-Specific High-Resolution Melting Curve analysis to evaluate the methylation of the selected promoter regions in converted genomic tissue DNA and plasma cfDNA. RESULTS: The methylation levels in selected regions of SPG20 (+24375 to +24680, +24209 to +24399, and +23625 to +23883), SNCA (+807 to +1013, +7 to +162, and -180 to +7), FBN1 (+223 to +429, +1 to +245, and -18 to -175), ITF2 (+296 to +436 and -180 to +55), SEPT9 (-914412 to -91590 and -99083 to -92264), and MLH1 (-13 to +22) were significantly higher in tumor tissues compared with normal adjacent tissues. The methylation levels of FBN1, ITF2, SNCA, and SPG20 promoters were significantly higher in the patient’s plasma compared to patient’s normal tissue and plasma of healthy control subjects. FBN1, SPG20, and SEPT9 promoter methylation had a good diagnostic performance for discriminating CRC tissues from normal adjacent tissues (AUC > 0.8). A panel of SPG20, FBN1, and SEPT9 methylation had a higher diagnostic value than that of any single biomarker and other panels in tissue-based assay (AUC > 0.9). The methylation of FBN1(a) and SPG20(a) regions, as the closest region to the first coding sequence (CDS), had a good diagnostic performance in plasma cfDNA (AUC > 0.8) while a panel consisted of FBN1(a) and SPG20(a) regions showed excellent diagnostic performance for CRC detection in plasma cfDNA (AUC > 0.9). CONCLUSION: Methylation of FBN1(a) and SPG20(a) promoter regions in the plasma cfDNA can be an excellent simple, non-invasive blood-based test for early detection of CRC.
Keywords: Colorectal neoplasm, DNA methylation, biomarkers, cell-free nucleic acids, liquid biopsy, fibrillin-1, SPG20 (Spastic paraplegia 20), ITF2 (Immunoglobulin transcription factor 2), SNCA (Synuclein alpha), RUNX3 (Runt-related transcription factor 3), SEPT9 (Septin 9), MLH1 (mutL homolog 1)
DOI: 10.3233/CBM-210315
Journal: Cancer Biomarkers, vol. 34, no. 2, pp. 221-250, 2022
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