<b>Identification and validation of the transcription factor RFX1 as a biomarker for prognosis and inflammatory infiltration in colon cancer</b>

<b>Purpose:</b> The difficulty in targeting colon cancer may be attributed to the plastic regulation of transcription factors. The transcription factor RFX1 exhibits a high degree of plasticity in inducing cancer cells with environment-dependent properties such as drug resistance, immunosuppression, or metastasis. However, the exploration of the relevance of RFX1 in the tumor microenvironment of colon cancer is still in its infancy.<b>Methods:</b> We have gradually focused our attention from pan-cancer to the molecular characterisation of RFX1 in colon cancer. We classified colon cancers into subgroups with high and low RFX1 expression and characterised their immune profiles, mutational profiles, cancer immunotherapy and drug sensitivity. Combining RFX1 expression and persistent tumor mutation burden, we innovatively propose a novel nomogram clinical prediction model and validate its function, and the correlation between high expression and poorer prognosis.<b>Results:</b> Compared to TMB, pTMB is an independent predictor of prognosis in colon cancer patients. Innovatively, the predictive efficacy of the combination of RFX1 and pTMB expression was more robust and sensitive compared to the effect of RFX1 combined with TMB. Among them, patients in the RFX1^high/pTMB^high subgroup had the worst quality of survival and prognosis, whereas patients in the RFX1^low/pTMB^low subgroup had a relatively better prognosis. Clinical tumor samples and immunohistochemical microarray results strongly validate the robust predictive potential of nomogram clinical models dependent on RFX1 and pTMB expression.<b>Conclusion:</b> A nomogram model based on the transcription factor RFX1 combined with pTMB provides an alternative approach to the diagnosis and treatment of colon cancer.

【研究目的】靶向结肠癌的难点可能归因于转录因子的可塑性调控。转录因子RFX1在诱导具有环境依赖性特性（如耐药性、免疫抑制或转移）的癌细胞时表现出高度的可塑性。然而，目前针对RFX1与结肠癌肿瘤微环境相关性的探索仍处于起步阶段。

【研究方法】本研究的关注重点逐步从泛癌（pan-cancer）分析转向结肠癌中RFX1的分子特征解析。我们将结肠癌患者分为RFX1高表达组与低表达组，并对两组的免疫谱、突变谱、癌症免疫治疗响应及药物敏感性进行了系统表征。结合RFX1表达水平与持续性肿瘤突变负荷（persistent tumor mutation burden, pTMB），本研究创新性地构建了一种新型列线图（nomogram）临床预测模型并验证其效能，同时证实了RFX1高表达与不良预后之间的相关性。

【研究结果】相较于肿瘤突变负荷（Tumor Mutation Burden, TMB），pTMB是结肠癌患者预后的独立预测因子。创新性地发现，相较于RFX1联合TMB的预测效果，RFX1与pTMB表达联合的预测效能更为稳健且灵敏。其中，RFX1^高表达/pTMB^高表达亚组患者的生存质量与预后最差，而RFX1^低表达/pTMB^低表达亚组患者的预后相对更佳。临床肿瘤样本与免疫组织化学微阵列（immunohistochemical microarray）结果有力验证了基于RFX1与pTMB表达的列线图临床模型所具备的稳健预测潜力。

【研究结论】基于转录因子RFX1联合pTMB构建的列线图模型，可为结肠癌的诊疗提供全新的备选方案。