Open Access

ARTICLE

RFX1 Regulates Immune Microenvironment and Predicts Immunotherapy Response in Colon Cancer: A Multi-Omics and Clinical Analysis

Zhujiang Dai^1,2,#, Xiaoyong Ge^1,2,#, Wenbo Tang^1,2, Chen-Ying Liu^1,2, Yun Liu^1,2,*, Zhongchuan Wang^1,2,*

1 Department of Colorectal Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200092, China
2 Shanghai Colorectal Cancer Research Center, Shanghai, 200092, China

* Corresponding Authors: Yun Liu. Email: ; Zhongchuan Wang. Email:
# These authors contributed equally to this work

(This article belongs to the Special Issue: Identification of potential targets and biomarkers for cancers and the exploration of novel molecular mechanisms of tumorigenesis and metastasis)

Oncology Research 2025, 33(12), 4113-4143. https://doi.org/10.32604/or.2025.068473

Received 30 May 2025; Accepted 18 August 2025; Issue published 27 November 2025

Abstract

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.

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