ArticleJournal of translational medicine2024
Identification of epigenetic silencing of the SFRP2 gene in colorectal cancer as a clinical biomarker and molecular significance.
Article in Journal of translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.
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Who cites it
8 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Mechanisms underlying obesity-malignancy connection: a systematic narrative review.Journal of physiology and biochemistry · 2025Pooled it
- Mitochondrial metabolite transporters at the crossroads of metabolic reprogramming, epigenetic regulation and therapeutic vulnerabilities in colorectal cancer.Molecular biology reports · 2026Review
- SFRP2 Potentiates Metastasis of Colon Cancer by Enhancing Snai1 Protein Stability via USP11.Journal of cellular and molecular medicine · 2026Article
- Epigenetic regulation of the β-catenin pathway in cadmium-induced colorectal cancer progression and chemoresistance.Frontiers in cell and developmental biology · 2026Review
- Secreted frizzled-related protein 2 as a context-dependent extracellular signaling hub in development, tissue remodeling, and disease.Frontiers in cell and developmental biology · 2026Review
- Single-Cell Sequencing Data Revealed Mechanisms of Interactions Between Tumor Cells and Cancer-Associated Fibroblasts in Metastatic Colorectal Cancer.BioMed research international · 2026Article
- Advances in colorectal cancer screening: technological innovations, guideline discrepancies, and individualized strategies.Frontiers in oncology · 2025Review
- Diagnostic potential of WNT signaling gene methylation in pulmonary tuberculosis.Frontiers in immunology · 2025Article
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9 authors.
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Abstract
backgroundSeveral studies have suggested secreted frizzled-related protein 2 (SFRP2) gene as a potential clinical biomarker in colorectal cancer (CRC). However, its diagnostic role remains unclear. In this study, we aimed to investigate the significance of SFRP2 methylation levels in a large cohort of biological specimens (including blood, adipose and colonic tissues) from patients with CRC, thereby potentially identifying new biomarker utility.
methodsWe examined the expression (by qPCR) and methylation status (by 450 K DNA array and DNA pyrosequencing) of the SFRP2 gene in healthy participants (N = 110, aged as 53.7 (14.2), 48/62 males/females) and patients with CRC (N = 85, aged 67.7 (10.5), 61/24 males/females), across different biological tissues, and assessing its potential as a biomarker for CRC. Additionally, we investigated the effect of recombinant human SFRP2 (rhSFRP2) as a therapeutic target, on cell proliferation, migration, and the expression of key genes related to carcinogenesis and the Wnt pathway.
resultsOur findings revealed that SFRP2 promoter methylation in whole blood could predict cancer stage (I + II vs. III + IV) (AUC = 0.653), lymph node invasion (AUC = 0.692), and CRC recurrence (AUC = 0.699) in patients with CRC (all with p < 0.05). Furthermore, we observed a global hypomethylation of SFRP2 in tumors compared to the adjacent area (p < 0.001). This observation was validated in the TCGA-COAD and TCGA-READ cohorts, demonstrating overall hypermethylation (both with p < 0.001) and low expression (p < 0.001), as shown in publicly available scRNA-Seq data. Notably, neoadjuvant-treated CRC patients exhibited lower SFRP2 methylation levels compared to untreated patients (p < 0.05) and low promoter SFRP2 methylation in untreated patients was associated with poor overall survival (p < 0.05), when compared to high methylation. Finally, treatment with 5 µg of rhSFRP2 treatment in CRC cells (HCT116 cells) inhibited cell proliferation (p < 0.001) and migration (p < 0.05), and downregulated the expression of AXIN2 (p < 0.01), a gene involved in Wnt signaling pathway.
conclusionsThese findings establish promoter methylation of the SFRP2 gene as a prognostic candidate in CRC when assessed in blood, and as a therapeutic prognostic candidate in tumors, potentially valuable in clinical practice. SFRP2 also emerges as a therapeutic option, providing new clinical and therapeutical avenues.
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