Radiation-Induced Lung Injury (RILI) is a significant complication arising from exposure to ionizing radiation, particularly in patients undergoing thoracic radiotherapy for cancer treatment. The incidence of RILI could reach as high as 30 %-50 % among patients receiving chest radiation, highlighting the critical need for effective management strategies (Arroyo-Hernández et al., 2021, Roy et al., 2021). This condition could progress to severe outcomes, including pulmonary fibrosis and respiratory failure, which are associated with high morbidity and mortality rates (Giuranno et al., 2019, Hanania et al., 2019, Xia et al., 2020). Current early diagnostic approaches (Chang et al., 2024, Wang et al., 2024) and effective targeted-drugs (Sheikholeslami et al., 2021) for RILI are limited. This highlights a long way to go in the identification of reliable early diagnostic biomarkers and effective therapeutic strategies of RILI.

The pathogenesis of RILI mainly includes the initial stages of oxidative stress and inflammatory response, followed by chronic tissue remodeling and fibrosis (Bakkal et al., 2013, Migdal and Serres, 2011, Terasaki et al., 2021). Ionizing radiation can induce the production of reactive oxygen species (ROS), leading to direct cell damage, activation of pro-inflammatory signaling pathways, and recruitment of immune cells (Albrecht et al., 2005, Mittal et al., 2014, Duecker et al., 2018, Fleckenstein et al., 2007, Kang et al., 2003). Continuous oxidative stress and dysregulation of inflammatory response play a central role in fibroblast activation and extracellular matrix deposition, ultimately leading to impaired lung function. Targeting the oxidative stress pathway may help slow down the progression of RILI, but its molecular mechanism has not been fully elucidated. This study aims to identify molecular features associated with oxidative stress and elucidate their roles in the occurrence and development of RILI by integrating bulk and single-cell RNA sequencing analysis, providing new insights for early diagnosis and targeted intervention.