TY - EJOU AU - Dai, Zhujiang AU - Ge, Xiaoyong AU - Tang, Wenbo AU - Liu, Chen-Ying AU - Liu, Yun AU - Wang, Zhongchuan TI - RFX1 Regulates Immune Microenvironment and Predicts Immunotherapy Response in Colon Cancer: A Multi-Omics and Clinical Analysis T2 - Oncology Research PY - 2025 VL - 33 IS - 12 SN - 1555-3906 AB - Objective: The plastic role of regulatory factor X1 (RFX1) in colon cancer progression and its impact on the tumor microenvironment remain poorly understood. The study aimed to clarify the molecular and clinical role of RFX1 in colon cancer. Methods: We classified colon cancers into subgroups with high and low RFX1 expression and characterized their immune profiles, mutational profiles, cancer immunotherapy and drug sensitivity. By combining RFX1 expression with persistent tumor mutational burden, we proposed a novel nomogram clinical prediction model and validated its predictive performance, and the correlation between high expression and poor prognosis. Results: Compared to tumor mutational burden (TMB), persistent tumor mutational burden (pTMB) is an independent predictor of prognosis in patients with colon cancer. The predictive efficacy of the combination of RFX1 expression and pTMB was superior to and sensitive than the combination of RFX1 expression with TMB. Among them, patients in the RFX1^high/pTMB^high subgroup had the worst quality of survival and prognosis, whereas those in the RFX1^low/pTMB^low subgroup had a relatively better prognosis (p < 0.0001). Univariate Cox regression revealed a significant association between high RFX1 expression and increased risk in colon cancer patients (Hazard Ratio [HR] = 1.58, 95% Confidence Interval [CI]: 1.10–2.25, p = 0.012), which remained independently predictive in multivariate analysis after covariate adjustment (HR = 1.52, 95% CI: 1.04–2.22, p = 0.031). Conclusion: A nomogram model based on RFX1 combined with pTMB provides an alternative approach for the diagnosis and treatment of colon cancer. KW - Colon cancer; regulatory factory X1; tumor microenvironment; persistent tumor mutational burden; pan-cancer DO - 10.32604/or.2025.068473