SFMBT2 hypermethylation promotes colorectal cancer progression and is a potential noninvasive biomarker for advanced CRC

The SFMBT2 protein is a Polycomb group protein implicated in transcriptional regulation and cancer biology. Here, we investigated the role of <i>SFMBT2</i> promoter hypermethylation in colorectal cancer (CRC) development and its clinical relevance. Using CRC cell lines, FFPE tissues, plasma samples, and public datasets, we show that promoter hypermethylation is associated with the transcriptional silencing of <i>SFMBT2</i>. <i>SFMBT2</i> expression was high in normal intestinal mucosa but progressively reduced in advanced adenoma, primary CRC, and metastatic lesions, accompanied by increased promoter methylation. Elevated plasma <i>SFMBT2</i> methylation was associated with higher recurrence risk in stage III CRC and poor prognosis in stage IV disease. Bioinformatic analyses further linked high <i>SFMBT2</i> expression to enhanced immune cell infiltration and activation of immune-related pathways. These findings identify <i>SFMBT2</i> hypermethylation as a potential noninvasive biomarker for recurrence risk stratification and prognostic assessment in advanced CRC, and suggest a role for <i>SFMBT2</i> in shaping the tumor immune microenvironment.