Wang Xuena, Yang Yang, Guo Hongxia, Li Xu, Sun Yue, Mei Qi, Ma Yuhui
Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.
Department of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.
Front Immunol. 2025 Jul 24;16:1573943. doi: 10.3389/fimmu.2025.1573943. eCollection 2025.
Immune-related pneumonitis (IRP) is a serious adverse event observed in lung adenocarcinoma patients undergoing immunotherapy. Previous studies have revealed that high Keratin 8 (KRT8) expression is associated with poor prognosis in these patients. However, the potential link between KRT8 expression levels and the risk of developing IRP remains unclear. This study aims to explore the correlation between KRT8 expression and IRP risk in lung adenocarcinoma patients receiving immunotherapy.
A case-control study was conducted involving 36 lung adenocarcinoma patients (12 IRP cases and 24 age- and sex-matched controls without IRP) receiving immunotherapy. Tumor tissue samples were analyzed for KRT8 expression using immunohistochemistry. A multivariate logistic regression analysis was performed to evaluate the relationship between KRT8 expression and IRP risk.
KRT8 expression was significantly higher in the IRP group compared to controls (12.9 ± 8.2% vs 5.6 ± 5.2%, adjusted = 0.03). Multivariate analysis revealed that each percentage increase in KRT8 expression was associated with a 32% increased risk of developing IRP (OR = 1.32, 95% CI: 1.09-1.61, = 0.005). Compared to the lowest tertile, the moderate KRT8 expression tertile showed no significant association with IRP risk, while the highest tertile demonstrated a significant 14-fold increased risk of developing IRP.
Elevated KRT8 expression in tumor tissues is significantly associated with increased IRP risk in lung adenocarcinoma patients receiving immunotherapy. These exploratory, hypothesis-generating findings suggest that KRT8 expression may serve as a potential biomarker for predicting IRP development, though validation in larger cohorts is needed.
免疫相关性肺炎（IRP）是接受免疫治疗的肺腺癌患者中观察到的一种严重不良事件。既往研究表明，高角蛋白8（KRT8）表达与这些患者的不良预后相关。然而，KRT8表达水平与发生IRP风险之间的潜在联系仍不清楚。本研究旨在探讨接受免疫治疗的肺腺癌患者中KRT8表达与IRP风险之间的相关性。
进行了一项病例对照研究，纳入36例接受免疫治疗的肺腺癌患者（12例IRP病例和24例年龄及性别匹配的无IRP对照）。采用免疫组织化学分析肿瘤组织样本中的KRT8表达。进行多因素逻辑回归分析以评估KRT8表达与IRP风险之间的关系。
与对照组相比，IRP组的KRT8表达显著更高（12.9±8.2%对5.6±5.2%，校正P=0.03）。多因素分析显示，KRT8表达每增加一个百分点，发生IRP的风险增加32%（OR=1.32，95%CI：1.09-1.61，P=0.005）。与最低三分位数相比，中等KRT8表达三分位数与IRP风险无显著关联，而最高三分位数显示发生IRP的风险显著增加14倍。
肿瘤组织中KRT8表达升高与接受免疫治疗的肺腺癌患者发生IRP的风险增加显著相关。这些探索性的、产生假设的发现表明，KRT8表达可能作为预测IRP发生的潜在生物标志物，尽管需要在更大队列中进行验证。
