An exploratory prognostic risk model for colon cancer developed from methylation-associated genes identified in circulating tumor cells
Year: 2026
Type: article
Abstract: Colon cancer (CRC) prognosis is closely associated with metastasis, with circulating tumor cells (CTCs) displaying DNA methylation abnormalities linked to metastatic behavior. This study aims to develop a risk model for CRC by utilizing methylation-associated genes identified from CTCs to predict prognosis and identify candidate compounds for pharmacologic investigation. RNA-Seq data, clinical information, and DNA methylation levels were sourced from GEO and TCGA databases. Differential gene expression analysis and intersections led to the identification of methylation-driven differentially expressed genes (MD-DEGs). Prognosis-related MD-DEGs (PMD-DEGs) were identified and employed to construct a CRC risk model, validated through risk assessments, survival analyses, receiver operating characteristic (ROC) curve evaluations, independent prognostic analyses, and an external cohort (GSE39582). Differences in drug sensitivity between high- and low-risk patients were also assessed. RT-qPCR, western blotting, and immunohistochemical analyses validated the PMD-DEGs. A total of 69 MD-DEGs were identified in the CRC cohort, with a risk model constructed incorporating five PMD-DEGs: IDUA, ELF5, ZBTB18, NOVA1, and TCEAL3. In the training cohort, the model stratified CRC patients by prognosis, although external validation revealed only limited discriminative capability. Computational drug-sensitivity analysis revealed predicted associations between these five PMD-DEGs and the sensitivity to 13 anticancer compounds. Additionally, RT-qPCR, western blotting, and immunohistochemistry confirmed significant differences in theexpression of these genes between CRC tissues and para-cancer normal (PCN) samples, and highlightedcandidate compounds warranting future experimental investigation.
Source: Discover Oncology
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $1,690
OpenAlex ID: W7223472570
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