TY - JOUR

T1 - Analysis of SDC2 and SEPT9 promoters methylation in plasma cfDNA to detect colorectal and precancerous lesions

AU - Borobova, Viktoria

AU - Aksamentov, Artem

AU - Sazonov, Dmitry

AU - Baklaushev, Vladimir

AU - Indinok, Dmitry

AU - Valuyskikh, Ekaterina

AU - Valuiskikh, Alexandr

AU - Oleynikova, Nina

AU - Laktionov, Petr

AU - Kovalenko, Sergey

PY - 2025/5/21

Y1 - 2025/5/21

N2 - Aim: Analysis of circulating free DNA (cfDNA) is now broadly used to diagnose, assess treatment response, and recurrence of various tumor types. Detection of aberrant cfDNA methylation in plasma is considered as one of the promising approaches for early-stage cancer detection, giving rise to new diagnostic tools. Colorectal cancer (CRC) has been one of the first malignancies for which relatively reliable diagnostic markers based on methylation analysis have been developed. Here, we aimed to assess the performance of SDC2 and SEPT9 promoter methylation in circulated plasma DNA as potential markers of colorectal precancerous lesions and carcinomas. Methods: Plasma samples were collected from donors with unknown cancer status and various anamnesis prior to colonoscopy. Methylation of SDC2 and SEPT9 genes promoters was blindly analyzed by multiplex methylation-specific PCR using Real-time-PCR-Sept9-SDC2-Met test (BioLink, Russia). Sensitivity, specificity, and AUC of SDC2 and SEPT9 tests were calculated for all groups of cancer and precancerous lesions. Results: Among 253 patients, 18 were diagnosed with CRC, 14 with advanced adenomas, and 17 with sessile serrated lesions according to the results of colonoscopy examination with subsequent biopsy. The plasma cell-free DNA test detected all cases of CRC, 11 out of 14 cases of advanced adenoma, and 10 out of 17 cases of sessile serrated lesions. The specificity of the SDC2 marker was 91.2% and 97.6% of SEPT9 marker. Conclusions: A minimal-invasive plasma test that detects methylated SDC2 and SEPT9 genes promoters might be considered as a screening method for detecting CRC and pre-cancerous lesions.

AB - Aim: Analysis of circulating free DNA (cfDNA) is now broadly used to diagnose, assess treatment response, and recurrence of various tumor types. Detection of aberrant cfDNA methylation in plasma is considered as one of the promising approaches for early-stage cancer detection, giving rise to new diagnostic tools. Colorectal cancer (CRC) has been one of the first malignancies for which relatively reliable diagnostic markers based on methylation analysis have been developed. Here, we aimed to assess the performance of SDC2 and SEPT9 promoter methylation in circulated plasma DNA as potential markers of colorectal precancerous lesions and carcinomas. Methods: Plasma samples were collected from donors with unknown cancer status and various anamnesis prior to colonoscopy. Methylation of SDC2 and SEPT9 genes promoters was blindly analyzed by multiplex methylation-specific PCR using Real-time-PCR-Sept9-SDC2-Met test (BioLink, Russia). Sensitivity, specificity, and AUC of SDC2 and SEPT9 tests were calculated for all groups of cancer and precancerous lesions. Results: Among 253 patients, 18 were diagnosed with CRC, 14 with advanced adenomas, and 17 with sessile serrated lesions according to the results of colonoscopy examination with subsequent biopsy. The plasma cell-free DNA test detected all cases of CRC, 11 out of 14 cases of advanced adenoma, and 10 out of 17 cases of sessile serrated lesions. The specificity of the SDC2 marker was 91.2% and 97.6% of SEPT9 marker. Conclusions: A minimal-invasive plasma test that detects methylated SDC2 and SEPT9 genes promoters might be considered as a screening method for detecting CRC and pre-cancerous lesions.

KW - Colorectal cancer

KW - advanced adenoma

KW - circulating tumor DNA test

KW - methylation

UR - https://www.mendeley.com/catalogue/8634a7a9-edbd-3f44-9e05-a6cb54d698a3/

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-105007210276&origin=inward&txGid=11a083dd7aff00023e373116c68dcad2

U2 - 10.37349/emed.2025.1001322

DO - 10.37349/emed.2025.1001322

M3 - Article

VL - 6

JO - Exploration of Medicine

JF - Exploration of Medicine

SN - 2692-3106

M1 - 1001322

ER -