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Abstract：
The clinical application and biological function of interferon regulatory factor 1 (IRF1) in non-small cell lung cancer (NSCLC) patients undergoing chemoimmunotherapy remain elusive. The aim of this study was to investigate the predictive and prognostic significance of IRF1 in NSCLC patients. We employed the cBioPortal database to predict frequency changes in IRF1 and explore its target genes. Bioinformatic methods were utilized to analyze the relationship between IRF1 and immune regulatory factors. Retrospective analysis of clinical samples was conducted to assess the predictive and prognostic value of IRF1 in chemoimmunotherapy. Additionally, A549 cells with varying IRF1 expression levels were constructed to investigate its effects on NSCLC cells, while animal experiments were performed to study the role of IRF1 in vivo. Our findings revealed that the primary mutation of IRF1 is deep deletion and it exhibits a close association with immune regulatory factors. KRAS and TP53 are among the target genes of IRF1, with interferon and IL-2 being the predominantly affected pathways. Clinically, IRF1 levels significantly correlate with the efficacy of chemoimmunotherapy. Patients with high IRF1 levels exhibited a median progression-free survival (mPFS) of 9.5 months, whereas those with low IRF1 levels had a shorter mPFS of 5.8 months. IRF1 levels positively correlate with PD-L1 distribution and circulating IL-2 levels. IL-2 enhances the biological function of IRF1 and recapitulates its role in vivo in the knockdown group. Therefore, IRF1 may possess predictive and prognostic value for chemoimmunotherapy in NSCLC patients through the regulation of the IL-2 inflammatory pathway.
摘要：
干扰素调节因子1(IRF1)在非小细胞肺癌(NSCLC)化疗中的临床应用及生物学功能研究尚不清楚。这项研究的目的是探讨IRF1在NSCLC患者中的预测和预后意义。我们使用cBioPortal数据库来预测IRF1的频率变化并探索其靶基因。采用生物信息学方法分析IRF1与免疫调节因子的关系。对临床样本进行回顾性分析，以评估IRF1在化学免疫治疗中的预测和预后价值。此外,构建具有不同IRF1表达水平的A549细胞以研究其对NSCLC细胞的影响。同时进行动物实验以研究IRF1在体内的作用。我们的发现表明IRF1的主要突变是深度缺失，并且与免疫调节因子密切相关。KRAS和TP53是IRF1的靶基因之一,其中干扰素和IL-2是主要受影响的途径。临床上,IRF1水平与化学免疫疗法的疗效显着相关。IRF1水平高的患者的中位无进展生存期（mPFS）为9.5个月，而IRF1水平低的患者的mPFS较短,为5.8个月.IRF1水平与PD-L1分布和循环IL-2水平呈正相关。IL-2增强了IRF1的生物学功能，并概括了其在敲除组中的体内作用。因此,IRF1可能通过调节IL-2炎症途径对NSCLC患者的化学免疫治疗具有预测和预后价值。
