Department of Respiratory Medicine, The First Affiliated Hospital of Jilin University, Jilin University, Changchun, Jilin, 130021, PR China.
Institute of Paediatrics, The First Affiliated Hospital of Jilin University, Jilin University, Changchun, Jilin, 130021, PR China.
Lung Cancer. 2019 Sep;135:47-55. doi: 10.1016/j.lungcan.2019.07.008. Epub 2019 Jul 9.
Non-small cell lung cancer (NSCLC) accounts for 85%-90% of lung cancer cases and is a covert disease lacking early symptoms. Since cancer is recognised as an inflammation-associated condition, we analysed the relationship between the expression of interferon regulatory factor 5 (IRF5), a key transcription factor controlling inflammatory responses, and NSCLC development with the aim of identifying a warning biomarker for early diagnosis of the disease.
The expression of IRF5 and its associated inflammatory factors IL-6, IL-10, IP-10, and TNF-α in the peripheral blood of NSCLC patients (n = 66) and healthy controls (n = 42) was analysed by quantitative RT-PCR, flow cytometry, and a cytometric bead array. IRF5 protein expression in NSCLC tissues (n = 102) was detected by Western blotting. The diagnostic value of IRF5 expression was determined by a receiver-operating characteristic (ROC) curve analysis.
The protein levels of IRF5, IL-6, and IP-10 were significantly higher in the peripheral blood of NSCLC patients than in that of healthy controls. IP-10 levels in plasma and IL-10 mRNA expression in white blood cells (WBCs) were significantly upregulated in early-stage NSCLC, whereas plasma IL-6 and IL-10 were elevated in the progressive stage. IRF5 protein levels in WBCs were positively correlated with plasma IP-10 but negatively correlated with plasma IL-10. Furthermore, the mRNA and protein levels of IRF5 in WBCs were significantly elevated in patients with early stage NSCLC compared to those in the progressive stage. Additionally, IRF5 protein levels were significantly lower in NSCLC tumour tissues than those in normal lung tissues.
IRF5 levels in WBCs can be significantly upregulated in early stage NSCLC and were shown to have diagnostic value as an early warning biomarker of NSCLC development.
非小细胞肺癌（NSCLC）占肺癌病例的 85%-90%，是一种缺乏早期症状的隐匿性疾病。由于癌症被认为是一种与炎症相关的疾病，我们分析了干扰素调节因子 5（IRF5）的表达与 NSCLC 发展之间的关系，IRF5 是控制炎症反应的关键转录因子，旨在确定一种用于早期诊断该疾病的预警生物标志物。
通过定量 RT-PCR、流式细胞术和细胞因子 bead 阵列分析了 NSCLC 患者（n=66）和健康对照者（n=42）外周血中 IRF5 及其相关炎症因子 IL-6、IL-10、IP-10 和 TNF-α的表达。采用 Western blot 检测 NSCLC 组织中 IRF5 蛋白的表达。通过受试者工作特征（ROC）曲线分析确定 IRF5 表达的诊断价值。
与健康对照组相比，NSCLC 患者外周血中 IRF5、IL-6 和 IP-10 的蛋白水平显著升高。早期 NSCLC 患者血浆 IP-10 水平和白细胞（WBC）中 IL-10 mRNA 表达显著上调，而进展期 NSCLC 患者血浆 IL-6 和 IL-10 水平升高。WBC 中 IRF5 蛋白水平与血浆 IP-10 呈正相关，与血浆 IL-10 呈负相关。此外，与进展期相比，早期 NSCLC 患者 WBC 中 IRF5 的 mRNA 和蛋白水平显著升高。此外，与正常肺组织相比，NSCLC 肿瘤组织中 IRF5 蛋白水平显著降低。
WBC 中 IRF5 水平在早期 NSCLC 中可显著上调，作为 NSCLC 发展的早期预警生物标志物具有诊断价值。
