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Abstract

Early Diagnosis of Colorectal Cancer via Plasma-Derived SDC2, KCNQ5, and IKZF1 Methylation Levels by Yi Zhang, Xiaoxiao Wang, Khan M. I. Sh, Yuwen Hao, Haiqiang Zhang, Shaofan Qiu, Haijun Wang, Zhanxue Zhang

Background: The incidence of colorectal cancer (CRC) is rapidly increasing, and early detection plays a crucial role in improving the prognosis and survival rates of patients. This study aimed to assess the diagnostic ability of combined SDC2-KCNQ5-IKZF1 methylation levels in plasma for CRC detection.
Methods: A total of 92 patients were recruited from the Department of General Surgery at the Second Hospital of Hebei Medical University, including 56 CRC patients, 22 polyp and adenoma patients, and 14 healthy controls. Plasma cfDNA was extracted for methylation test of SDC2, KCNQ5, and IKZF1. Sanger sequencing was conducted to verify the methylation results. The performance of single-gene methylation and triple-gene methylation combined test were analyzed. The positive detection rates of methylation and CEA test were compared to the colonoscopy gold standard. ROC curve was utilized to evaluate the diagnostic value in CRC.
Results: The positive detection rates of triple-gene tests in CRC and precancerous lesions were 87.50% and 95.45%, respectively. The triple-gene test performed better than single-gene or CEA test. Combined analysis of triple-gene and CEA test could further improve the detection rate. Univariate analysis showed no statistical correlation between the methylation levels and patients' gender, age, history of diabetes, tumor site, lymph node metastasis, and tumor stage. In ROC curve analysis, AUC areas of SDC2, KCNQ5, and IKZF1 were 0.700, 0.646, and 0.645, respectively. The AUC area of triple-gene test was 0.924.
Conclusions: The triple-gene combined methylation test demonstrated excellent diagnostic performance for CRC and precancerous lesions.

DOI: 10.7754/Clin.Lab.2024.240146