Identification and exploration of key genes associated with radioresistance in lung adenocarcinoma

作者：Ying Wang, Yangyang Shang, Mingyu Hua, Yidi Wang, Beina Hui, Weibin Hu, Mengke Zhu, Xiaozhi Zhang, Jing Li · 发表于：Cancer Cell International · 年份：2025 · DOI：10.1186/s12935-025-03783-1 · 被引用次数：5 · 研究领域：Effects of Radiation Exposure、Ferroptosis and cancer prognosis、Genomics and Chromatin Dynamics

BACKGROUND: Radiation resistance in lung adenocarcinoma (LUAD) remains a primary obstacle limiting radiotherapy efficacy. However, the detailed factors and molecular mechanisms influencing LUAD radiosensitivity are not fully understood. METHODS: Radioresistance-related genes (RRRGs) were screened by RNA sequencing and bioinformatics analysis, and a prediction model for radiotherapy efficacy was developed via LASSO-Cox regression analysis. We specifically focused on Stanniocalcin 2 (STC2) due to its prognostic significance and validated its expression through immunohistochemical staining (IHC) in pathological samples from LUAD patients. A STC2 knockdown (siSTC2) A549 cell line was created, and Western blotting, CCK8, and colony formation assays were performed to investigate STC2's involvement in radioresistance. RESULTS: An efficacy prediction model was constructed using 6 RRRGs (FCGBP, SLCO4A1, ALDH3A1, STC2, TERT, CYP24A1). IHC analysis of 74 LUAD patients showed significantly higher STC2 expression in radiotherapy non-responders (N-Res) versus responders (Res) (p < 0.05). Patients with elevated STC2 levels experienced shorter overall survival (OS). Western blotting revealed higher STC2 expression in irradiated (IR) A549 cells compared to non-irradiated (N-IR) (p < 0.05). CCK8 assays results suggested that knockdown of STC2 resulted in a significant reduction in cell proliferation ability (p < 0.05), and colony formation assays confirmed a significant decrease in clonogenic ...