Lv Jie, Yu Chun-Yang, Xiong Yao-Zu, Dai Ting-Ting, Hu Xiao-Chu, Pan Peng, Yue Shun, Yu Chang-Hua
Department of Radiotherapy, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an, China.
Department of Cardiology, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an, China.
Front Immunol. 2025 May 29;16:1574113. doi: 10.3389/fimmu.2025.1574113. eCollection 2025.
A significant challenge in treating non-small cell lung cancer (NSCLC) is its inherent resistance to radiation therapy, leading to poor patient prognosis. This study aimed to identify key genes influencing radiotherapy resistance in NSCLC through comprehensive bioinformatics analysis.
A total of 103 common genes were identified, enriched in critical biological pathways such as coagulation, complement activation, growth factor activity, and cytokine signaling. Using advanced machine learning techniques like SVM-RFE, LASSO regression, and random forest algorithms, four pivotal genes-TGFBI, FAS, PTK6, and FA2H-were identified.
TGFBI showed the strongest correlation with NSCLC prognosis as indicated by a diagnostic nomogram. Additionally, significant differences in immune cell infiltration, particularly involving naive B cells and M0 macrophages, were noted between high-risk and low-risk patients.
The study suggests that targeting pathways regulating macrophage polarization or enhancing naive B cell activation could play a crucial role in addressing radiotherapy resistance. The findings highlight the potential therapeutic targets, thereby advancing the understanding of the molecular mechanisms underlying radiotherapy resistance in NSCLC, with implications for improving patient management and outcomes.
治疗非小细胞肺癌（NSCLC）的一个重大挑战是其对放射治疗固有的抗性，导致患者预后不良。本研究旨在通过全面的生物信息学分析，确定影响NSCLC放疗抗性的关键基因。
共鉴定出103个常见基因，这些基因富集于凝血、补体激活、生长因子活性和细胞因子信号传导等关键生物学途径。使用支持向量机递归特征消除（SVM-RFE）、套索回归和随机森林算法等先进的机器学习技术，确定了四个关键基因——TGFBI、FAS、PTK6和FA2H。
诊断列线图显示，TGFBI与NSCLC预后的相关性最强。此外，高风险和低风险患者之间在免疫细胞浸润方面存在显著差异，尤其是幼稚B细胞和M0巨噬细胞。
该研究表明，靶向调节巨噬细胞极化的途径或增强幼稚B细胞活化可能在解决放疗抗性方面发挥关键作用。这些发现突出了潜在的治疗靶点，从而加深了对NSCLC放疗抗性分子机制的理解，对改善患者管理和治疗结果具有重要意义。
