ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1573943
This article is part of the Research TopicExploring Adverse Drug Reactions: Monitoring, Mechanism, Intervention, and ResolutionView all 6 articles
Association Between Keratin 8 Expression and Immune-Related Pneumonitis: A Case-Control Study in Lung Adenocarcinoma Patients
Provisionally accepted
- 1Shanxi Bethune Hospital, Shanxi Medical University, Taiyuan, China
- 2Guangdong Provincial People's Hospital, Guangzhou, Guangdong Province, China
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Background: 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.Methods: 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.Results: KRT8 expression was significantly higher in the IRP group compared to controls (12.9 ± 8.2% vs 5.6 ± 5.2%, adjusted P = 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, P = 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.Conclusion: 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.
Keywords: Immune-related pneumonitis, Keratin 8, Lung Adenocarcinoma, case-control, lung cancer
Received: 10 Feb 2025; Accepted: 07 Jul 2025.
Copyright: © 2025 Wang, Guo, Li, Sun and Ma. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yuhui Ma, Shanxi Bethune Hospital, Shanxi Medical University, Taiyuan, China
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