Li Gang, Cui Jingmin, He Shuang, Feng Xiufang, Li Wenhan, Li Tao, Chen Peilin
Department of Urology, Tangshan Gongren Hospital, 27 Wenhua Road, Tangshan, 063000, Hebei, China.
Tangshan Lunan District First Nursery Center (Lunan District First Kindergarten), China.
Heliyon. 2024 Oct 5;10(20):e39021. doi: 10.1016/j.heliyon.2024.e39021. eCollection 2024 Oct 30.
Increasing evidence indicates that RNA modifications are misregulated in human cancers, which might be optimal targets of cancer therapy. However, important RNA regulators in kidney cancer still need further exploration. In this study, we collected regulators representing different types of RNA modification and identified the prognosis-related RNA regulators in kidney cancer patients. We further constructed a 4-gene RNA regulators signature and index called prognosis-related RNA regulators index (PRRI) by the Lasso-Cox regression algorithm. We found that PRRI could precisely predict prognosis of patients in the KIRC training (AUC at 3-/5-/7-years = 0.7132/0.7220/0.7283) and testing cohorts (AUC at 3-/5-/7-years = 0.7141/0.7403/0.7305) and two independent RCC cohorts - E-MTAB-1980 (AUC at 3-/5-/7-years = 0.7036/0.7385/0.7143) and KIRP (AUC at 3-/5-/7-years = 0.6203/0.6365/0.6941). Moreover, the high PRRI group showed a worse clinical outcome than the low PRRI group. PRRI demonstrated strong robustness and was related to histological grade and pathologic stage, which was also found to be an independent prognosis factor when other clinical variables adjusted it. We further found several immune-related pathways differentially enriched in the high or low PRRI group. The regulation of T cell migration, which has been proven to be an immunosuppressive cell, shows a high enrichment in the high PRRI group. Further analysis reveals that PRRI also shows a highly positive correlation with the activity of Tregs. TIDE analysis and two independent immune therapy cohorts revealed that the high PRRI group might resist immune therapy, while the low PRRI group might benefit from the treatment, indicating that PRRI could be a marker for predicting immune therapeutic response. All in all, we determined 4 potentially essential RNA regulators and illustrated their mechanisms concretely. Furthermore, we constructed a 4-gene index called PRRI to predict patients' outcomes and immunotherapy response.
越来越多的证据表明，RNA修饰在人类癌症中存在失调，这可能是癌症治疗的理想靶点。然而，肾癌中重要的RNA调节因子仍需进一步探索。在本研究中，我们收集了代表不同类型RNA修饰的调节因子，并鉴定了肾癌患者中与预后相关的RNA调节因子。我们进一步通过Lasso-Cox回归算法构建了一个名为预后相关RNA调节因子指数（PRRI）的4基因RNA调节因子特征和指数。我们发现PRRI可以精确预测KIRC训练队列（3/5/7年时的AUC = 0.7132/0.7220/0.7283）和测试队列（3/5/7年时的AUC = 0.7141/0.7403/0.7305）以及两个独立的RCC队列——E-MTAB-1980（3/5/7年时的AUC = 0.7036/0.7385/0.7143）和KIRP（3/5/7年时的AUC = 0.6203/0.6365/0.6941）中患者的预后。此外，高PRRI组的临床结局比低PRRI组更差。PRRI表现出很强的稳健性，并且与组织学分级和病理分期相关，当对其他临床变量进行调整时，它也是一个独立的预后因素。我们进一步发现几个免疫相关通路在高或低PRRI组中存在差异富集。已被证明是免疫抑制细胞的T细胞迁移调节在高PRRI组中高度富集。进一步分析表明，PRRI与调节性T细胞的活性也呈高度正相关。TIDE分析和两个独立的免疫治疗队列显示，高PRRI组可能对免疫治疗有抗性，而低PRRI组可能从治疗中获益，这表明PRRI可能是预测免疫治疗反应的一个标志物。总而言之，我们确定了4个潜在的关键RNA调节因子并具体阐述了它们的机制。此外，我们构建了一个名为PRRI的4基因指数来预测患者的预后和免疫治疗反应。
