多项研究表明，分泌型卷曲相关蛋白 2 (SFRP2) 基因可作为结直肠癌 (CRC) 的潜在临床生物标志物。然而，其诊断作用仍不清楚。在本研究中，我们旨在调查 CRC 患者的大量生物样本（包括血液、脂肪和结肠组织）中 SFRP2 甲基化水平的意义，从而有可能确定新的生物标志物实用性。我们检查了表达（通过 qPCR）健康参与者（N = 110，年龄为 53.7 (14.2)，48/62 男性/女性）和 CRC 患者（N = 85，年龄 67.7）SFRP2 基因的甲基化状态（通过 450 K DNA 阵列和 DNA 焦磷酸测序） （10.5），61/24 男性/女性），跨越不同的生物组织，并评估其作为 CRC 生物标志物的潜力。此外，我们研究了重组人 SFRP2 (rhSFRP2) 作为治疗靶点对细胞增殖、迁移以及与癌发生和 Wnt 通路相关的关键基因表达的影响。我们的研究结果表明，全血中的 SFRP2 启动子甲基化可以预测CRC患者的癌症分期（I  II与III  IV）（AUC = 0.653）、淋巴结侵犯（AUC = 0.692）和CRC复发（AUC = 0.699）（均p< 0.05）。此外，我们观察到与邻近区域相比，肿瘤中 SFRP2 的整体低甲基化（p < 0.001）。这一观察结果在 TCGA-COAD 和 TCGA-READ 队列中得到了验证，证明了总体高甲基化（均 p<0.001）和低表达（p<0.001），如公开的 scRNA-Seq 数据所示。值得注意的是，与未治疗的患者相比，新辅助治疗的 CRC 患者表现出较低的 SFRP2 甲基化水平 (p<0.05)，并且与高甲基化相比，未治疗患者的低启动子 SFRP2 甲基化与较差的总生存率相关 (p<0.05)。最后，在 CRC 细胞（HCT116 细胞）中使用 5 µg rhSFRP2 处理可抑制细胞增殖 (p < 0.001) 和迁移 (p < 0.05)，并下调 AXIN2（一种参与 Wnt 信号传导的基因）的表达 (p < 0.01)这些发现确立了 SFRP2 基因的启动子甲基化在血液中评估时可作为 CRC 的预后候选者，并作为肿瘤的治疗性预后候选者，在临床实践中具有潜在价值。 SFRP2 也作为一种治疗选择出现，提供了新的临床和治疗途径。© 2024。作者。

Several 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.We 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.Our 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.These 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.© 2024. The Author(s).