# SFMBT2 hypermethylation promotes colorectal cancer progression and is a potential noninvasive biomarker for advanced CRC **Authors:** Wei Wang, Ling Yu, Wenyuan He, Jingyi Wu, Yuansen Li, Wenzhi Cui, Danli Ye, Juan Zhou, Ming Xie, Xuwen Lai, Chengyong Lei PMC · DOI: 10.1016/j.isci.2026.115019 · iScience · 2026-02-13 ## TL;DR This study shows that SFMBT2 gene hypermethylation is linked to colorectal cancer progression and could serve as a noninvasive biomarker for predicting outcomes in advanced CRC. ## Contribution The study identifies SFMBT2 hypermethylation as a novel noninvasive biomarker for advanced CRC prognosis and recurrence risk. ## Key findings - Promoter hypermethylation of SFMBT2 leads to its transcriptional silencing in CRC. - Plasma SFMBT2 methylation levels correlate with recurrence risk in stage III CRC and poor prognosis in stage IV CRC. - High SFMBT2 expression is associated with immune cell infiltration and immune-related pathways in CRC. ## Abstract The SFMBT2 protein is a Polycomb group protein implicated in transcriptional regulation and cancer biology. Here, we investigated the role of SFMBT2 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 SFMBT2. SFMBT2 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 SFMBT2 methylation was associated with higher recurrence risk in stage III CRC and poor prognosis in stage IV disease. Bioinformatic analyses further linked high SFMBT2 expression to enhanced immune cell infiltration and activation of immune-related pathways. These findings identify SFMBT2 hypermethylation as a potential noninvasive biomarker for recurrence risk stratification and prognostic assessment in advanced CRC, and suggest a role for SFMBT2 in shaping the tumor immune microenvironment. •SFMBT2 promoter hypermethylation drives transcriptional silencing in CRC•SFMBT2 expression decreases from adenoma to metastatic CRC•Plasma SFMBT2 methylation predicts recurrence and prognosis in advanced CRC•SFMBT2 expression correlates with immune infiltration and immune pathways SFMBT2 promoter hypermethylation drives transcriptional silencing in CRC SFMBT2 expression decreases from adenoma to metastatic CRC Plasma SFMBT2 methylation predicts recurrence and prognosis in advanced CRC SFMBT2 expression correlates with immune infiltration and immune pathways Diagnostics; Cancer ## Linked entities - **Genes:** SFMBT2 (Scm like with four mbt domains 2) [NCBI Gene 57713] - **Proteins:** SFMBT2 (Scm like with four mbt domains 2) - **Diseases:** colorectal cancer (MONDO:0005575), CRC (MONDO:0005575) ## Full-text entities - **Genes:** CDKN2A (cyclin dependent kinase inhibitor 2A) [NCBI Gene 1029] {aka ARF, CAI2, CDK4I, CDKN2, CMM2, INK4}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, SFRP2 (secreted frizzled related protein 2) [NCBI Gene 6423] {aka FRP-2, SARP1, SDF-5}, TENM1 (teneurin transmembrane protein 1) [NCBI Gene 10178] {aka ODZ1, ODZ3, TEN-M1, TEN1, TNM, TNM1}, PSG2 (pregnancy specific beta-1-glycoprotein 2) [NCBI Gene 5670] {aka CEA, PSBG2, PSG1}, GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 2597] {aka G3PD, GAPD, HEL-S-162eP}, MGMT (O-6-methylguanine-DNA methyltransferase) [NCBI Gene 4255], CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, WIF1 (Wnt inhibitory factor 1) [NCBI Gene 11197] {aka WIF-1}, NPY (neuropeptide Y) [NCBI Gene 4852] {aka PYY4}, APC (APC regulator of Wnt signaling pathway) [NCBI Gene 324] {aka BTPS2, DESMD, DP2, DP2.5, DP3, GS}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, HLTF (helicase like transcription factor) [NCBI Gene 6596] {aka HIP116, HIP116A, HLTF1, RNF80, SMARCA3, SNF2L3}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, SFMBT2 (Scm like with four mbt domains 2) [NCBI Gene 57713], MMP26 (matrix metallopeptidase 26) [NCBI Gene 56547], HPP1 [NCBI Gene 780897], MMP9 (matrix metallopeptidase 9) [NCBI Gene 4318] {aka CLG4B, GELB, MANDP2, MMP-9} - **Diseases:** I-II (MESH:D056829), stage (MESH:D062706), OPSCC (MESH:D000077195), clear cell renal cell carcinoma (MESH:D002292), lymph node metastases (MESH:D008207), breast, lung, gastric, renal, and esophageal cancers (MESH:D013274), IV (MESH:D006011), colorectal tumorigenesis (MESH:D063646), CIMP (MESH:D007516), adenoma (MESH:D000236), stage III disease (MESH:D007676), Cancer (MESH:D009369), metastatic disease (MESH:D000092182), prostate cancer (MESH:D011471), hepatic metastasis (MESH:D009362), dysplasia (MESH:D015792), CRC (MESH:D015179), /II (MESH:C537730), AA (MESH:C566236) - **Chemicals:** PBS (MESH:D007854), 5-aza-2'-deoxycytidine (MESH:D000077209), CO2 (MESH:D002245), Trizol (MESH:C411644), chloroform (MESH:D002725), OMIX014633 (-), penicillin (MESH:D010406) - **Species:** Mycoplasma (genus) [taxon 2093], Homo sapiens (human, species) [taxon 9606], Human papillomavirus (species) [taxon 10566] - **Cell lines:** HT29 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0320), Lovo — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0399), FHC — Homo sapiens (Human), Spontaneously immortalized cell line (CVCL_3688), SW480 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0546), SW620 — Homo sapiens (Human), Colon adenocarcinoma, Cancer cell line (CVCL_0547) ## Full text _Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC12969127/full.md ## Figures 7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12969127/full.md ## References 42 references — full list in the complete paper: https://tomesphere.com/paper/PMC12969127/full.md --- Source: https://tomesphere.com/paper/PMC12969127