Diagnostic value of CEACAM6 and HE4 in pleural fluid for malignant pleural effusion

Objective This study aimed to assess the diagnostic performance of carcinoembryonic antigen-related adhesion molecule 6 (CEACAM6) and human epididymis protein 4 (HE4) in pleural fluid for the detection of malignant pleural effusion (MPE).Materials and methods In this prospective study, pleural level...

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Main Authors: Jie Li, Liyuan Lin, Shengrui Yang, Yuan Mu, Lixia Zhang, Haoyu Ruan, Jian Xu
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Annals of Medicine
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Online Access:https://www.tandfonline.com/doi/10.1080/07853890.2025.2489748
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author Jie Li
Liyuan Lin
Shengrui Yang
Yuan Mu
Lixia Zhang
Haoyu Ruan
Jian Xu
author_facet Jie Li
Liyuan Lin
Shengrui Yang
Yuan Mu
Lixia Zhang
Haoyu Ruan
Jian Xu
author_sort Jie Li
collection DOAJ
description Objective This study aimed to assess the diagnostic performance of carcinoembryonic antigen-related adhesion molecule 6 (CEACAM6) and human epididymis protein 4 (HE4) in pleural fluid for the detection of malignant pleural effusion (MPE).Materials and methods In this prospective study, pleural levels of CEACAM6 and HE4 were measured in two independent cohorts. The test cohort included 182 patients with exudative pleural effusions (123 malignant and 59 benign), and the validation cohort comprised 117 patients with exudative pleural effusions (65 malignant and 52 benign). Receiver operating characteristic (ROC) curves were used to assess the diagnostic performance of CEACAM6 and HE4 for MPE.Results Both CEACAM6 and HE4 levels were significantly elevated in MPE compared to benign pleural effusion (BPE) in both cohorts (p < .001). In the test cohort, CEACAM6 and HE4 demonstrated areas under the curve (AUC) values of 0.862 and 0.826, respectively. The combination of CEACAM6 and HE4 yielded a higher AUC of 0.938 compared to either marker alone. In the validation cohort, both CEACAM6 (AUC = 0.811) and HE4 (AUC = 0.721), along with their combination (AUC = 0.834), exhibited strong diagnostic performance for MPE. Notably, in cytology-negative cases, the combination of CEACAM6 and HE4 also demonstrated a favourable diagnostic efficacy, with an AUC of 0.800. The addition of CEA to the CEACAM6/HE4 combination further improved the AUC to 0.819 (p = .04).Conclusions Pleural CEACAM6 and HE4 are promising biomarkers for distinguishing MPE from BPE. Their combination improves diagnostic accuracy, offering a valuable tool for MPE diagnosis, especially in challenging cases with cytology-negative pleural effusion.
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spelling doaj-art-16653e53ddfc4cd7a374e675d37eca9c2025-08-20T02:16:14ZengTaylor & Francis GroupAnnals of Medicine0785-38901365-20602025-12-0157110.1080/07853890.2025.2489748Diagnostic value of CEACAM6 and HE4 in pleural fluid for malignant pleural effusionJie Li0Liyuan Lin1Shengrui Yang2Yuan Mu3Lixia Zhang4Haoyu Ruan5Jian Xu6Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, ChinaObjective This study aimed to assess the diagnostic performance of carcinoembryonic antigen-related adhesion molecule 6 (CEACAM6) and human epididymis protein 4 (HE4) in pleural fluid for the detection of malignant pleural effusion (MPE).Materials and methods In this prospective study, pleural levels of CEACAM6 and HE4 were measured in two independent cohorts. The test cohort included 182 patients with exudative pleural effusions (123 malignant and 59 benign), and the validation cohort comprised 117 patients with exudative pleural effusions (65 malignant and 52 benign). Receiver operating characteristic (ROC) curves were used to assess the diagnostic performance of CEACAM6 and HE4 for MPE.Results Both CEACAM6 and HE4 levels were significantly elevated in MPE compared to benign pleural effusion (BPE) in both cohorts (p < .001). In the test cohort, CEACAM6 and HE4 demonstrated areas under the curve (AUC) values of 0.862 and 0.826, respectively. The combination of CEACAM6 and HE4 yielded a higher AUC of 0.938 compared to either marker alone. In the validation cohort, both CEACAM6 (AUC = 0.811) and HE4 (AUC = 0.721), along with their combination (AUC = 0.834), exhibited strong diagnostic performance for MPE. Notably, in cytology-negative cases, the combination of CEACAM6 and HE4 also demonstrated a favourable diagnostic efficacy, with an AUC of 0.800. The addition of CEA to the CEACAM6/HE4 combination further improved the AUC to 0.819 (p = .04).Conclusions Pleural CEACAM6 and HE4 are promising biomarkers for distinguishing MPE from BPE. Their combination improves diagnostic accuracy, offering a valuable tool for MPE diagnosis, especially in challenging cases with cytology-negative pleural effusion.https://www.tandfonline.com/doi/10.1080/07853890.2025.2489748CEACAM6HE4malignant pleural effusiondiagnosissensitivityspecificity
spellingShingle Jie Li
Liyuan Lin
Shengrui Yang
Yuan Mu
Lixia Zhang
Haoyu Ruan
Jian Xu
Diagnostic value of CEACAM6 and HE4 in pleural fluid for malignant pleural effusion
Annals of Medicine
CEACAM6
HE4
malignant pleural effusion
diagnosis
sensitivity
specificity
title Diagnostic value of CEACAM6 and HE4 in pleural fluid for malignant pleural effusion
title_full Diagnostic value of CEACAM6 and HE4 in pleural fluid for malignant pleural effusion
title_fullStr Diagnostic value of CEACAM6 and HE4 in pleural fluid for malignant pleural effusion
title_full_unstemmed Diagnostic value of CEACAM6 and HE4 in pleural fluid for malignant pleural effusion
title_short Diagnostic value of CEACAM6 and HE4 in pleural fluid for malignant pleural effusion
title_sort diagnostic value of ceacam6 and he4 in pleural fluid for malignant pleural effusion
topic CEACAM6
HE4
malignant pleural effusion
diagnosis
sensitivity
specificity
url https://www.tandfonline.com/doi/10.1080/07853890.2025.2489748
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