Liu Youyi, Wu Mengdi, Guo Jingrou, Tang Yifei, Jiang Hongliang, Yang Bo, Wu Minchen, Huang Jianfeng
Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China.
Department of Radiation Oncology, Affiliated Hospital of Jiangnan University, Wuxi 214122, China.
J Clin Med. 2023 Jan 17;12(3):733. doi: 10.3390/jcm12030733.
Radiation-induced lung injury (RILI), a potentially fatal and dose-limiting complication of radiotherapy for thoracic tumors, is divided into early reversible pneumonitis and irreversible advanced-stage fibrosis. Early detection and intervention contribute to improving clinical outcomes of patients. However, there is still a lack of reliable biomarkers for early prediction and clinical diagnosis of RILI. Given the central role of inflammation in the initiation and progression of RILI, we explored specific inflammation-related biomarkers during the development of RILI in this study. Two expression profiles from the Gene Expression Omnibus (GEO) database were downloaded, in which 75 differentially expressed genes (DEGs) were screened out. Combining Gene Oncology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and protein-protein interaction (PPI) network analysis, we identified four inflammation-related hub genes in the progression of RILI-MMP9, IL-1β, CCR1 and S100A9. The expression levels of the hub genes were verified in RILI mouse models, with S100A9 showing the highest level of overexpression. The level of S100A9 in bronchoalveolar lavage fluid (BALF) and the expression of S100A9 in lung tissues were positively correlated with the degree of inflammation in RILI. The results above indicate that S100A9 is a potential biomarker for the early prediction and diagnosis of the development of RILI.
放射性肺损伤(RILI)是胸部肿瘤放疗中一种潜在致命且限制剂量的并发症,分为早期可逆性肺炎和不可逆的晚期纤维化。早期检测和干预有助于改善患者的临床结局。然而,对于RILI的早期预测和临床诊断,仍然缺乏可靠的生物标志物。鉴于炎症在RILI发生和发展中的核心作用,我们在本研究中探索了RILI发展过程中特定的炎症相关生物标志物。从基因表达综合数据库(GEO)下载了两个表达谱,从中筛选出75个差异表达基因(DEG)。结合基因本体论(GO)、京都基因与基因组百科全书(KEGG)分析以及蛋白质-蛋白质相互作用(PPI)网络分析,我们在RILI进展过程中鉴定出四个炎症相关的枢纽基因——基质金属蛋白酶9(MMP9)、白细胞介素-1β(IL-1β)、C-C趋化因子受体1(CCR1)和钙结合蛋白S100A9。在RILI小鼠模型中验证了枢纽基因的表达水平,其中S100A9的过表达水平最高。支气管肺泡灌洗液(BALF)中S100A9的水平以及肺组织中S100A9的表达与RILI的炎症程度呈正相关。上述结果表明,S100A9是RILI发生发展早期预测和诊断的潜在生物标志物。