Association between keratin 8 expression and immune-related pneumonitis: a case-control study in lung adenocarcinoma patients

BackgroundImmune-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...

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Main Authors: Xuena Wang, Yang Yang, Hongxia Guo, Xu Li, Yue Sun, Qi Mei, Yuhui Ma
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Immunology
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Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2025.1573943/full
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author Xuena Wang
Yang Yang
Hongxia Guo
Xu Li
Yue Sun
Qi Mei
Yuhui Ma
author_facet Xuena Wang
Yang Yang
Hongxia Guo
Xu Li
Yue Sun
Qi Mei
Yuhui Ma
author_sort Xuena Wang
collection DOAJ
description BackgroundImmune-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.MethodsA 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.ResultsKRT8 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.ConclusionElevated 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.
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spelling doaj-art-943226c8f31b439b8da36015c149a0aa2025-08-20T03:32:19ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.15739431573943Association between keratin 8 expression and immune-related pneumonitis: a case-control study in lung adenocarcinoma patientsXuena Wang0Yang Yang1Hongxia Guo2Xu Li3Yue Sun4Qi Mei5Yuhui Ma6Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, ChinaDepartment of Ophthalmology, Renmin Hospital of Wuhan University, Wuhan, Hubei, ChinaShanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, ChinaShanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, ChinaDepartment of Endoscopy, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, ChinaDepartment of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, ChinaShanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi, ChinaBackgroundImmune-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.MethodsA 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.ResultsKRT8 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.ConclusionElevated 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.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1573943/fullimmune-related pneumonitiskeratin 8lung adenocarcinomacase-controllung cancer
spellingShingle Xuena Wang
Yang Yang
Hongxia Guo
Xu Li
Yue Sun
Qi Mei
Yuhui Ma
Association between keratin 8 expression and immune-related pneumonitis: a case-control study in lung adenocarcinoma patients
Frontiers in Immunology
immune-related pneumonitis
keratin 8
lung adenocarcinoma
case-control
lung cancer
title Association between keratin 8 expression and immune-related pneumonitis: a case-control study in lung adenocarcinoma patients
title_full Association between keratin 8 expression and immune-related pneumonitis: a case-control study in lung adenocarcinoma patients
title_fullStr Association between keratin 8 expression and immune-related pneumonitis: a case-control study in lung adenocarcinoma patients
title_full_unstemmed Association between keratin 8 expression and immune-related pneumonitis: a case-control study in lung adenocarcinoma patients
title_short Association between keratin 8 expression and immune-related pneumonitis: a case-control study in lung adenocarcinoma patients
title_sort association between keratin 8 expression and immune related pneumonitis a case control study in lung adenocarcinoma patients
topic immune-related pneumonitis
keratin 8
lung adenocarcinoma
case-control
lung cancer
url https://www.frontiersin.org/articles/10.3389/fimmu.2025.1573943/full
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