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Diagnostic value of CEACAM6 and HE4 in pleural fluid for malignant pleural effusion
Jie Li1,2, Liyuan Lin1,2, Shengrui Yang1,2
1Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
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.
Insights
Carcinoembryonic antigen-related adhesion molecule 6 (CEACAM6) and human epididymis protein 4 (HE4) show promise as biomarkers for diagnosing malignant pleural effusion (MPE). Combining CEACAM6 and HE4 significantly improves diagnostic accuracy, especially in difficult cytology-negative cases.
Area of Science:
- Oncology
- Biomarker Discovery
- Diagnostic Medicine
Background:
- Malignant pleural effusion (MPE) diagnosis can be challenging, often requiring invasive procedures.
- Accurate differentiation between malignant and benign pleural effusion (BPE) is crucial for patient management.
- Novel biomarkers are needed to improve the diagnostic accuracy of MPE.
Purpose of the Study:
- To evaluate the diagnostic performance of carcinoembryonic antigen-related adhesion molecule 6 (CEACAM6) and human epididymis protein 4 (HE4) in pleural fluid for MPE detection.
- To assess the combined diagnostic utility of CEACAM6 and HE4.
- To investigate their efficacy in cytology-negative MPE cases.
Main Methods:
- Prospective study involving two independent cohorts of patients with exudative pleural effusions.
- Measurement of pleural fluid levels of CEACAM6 and HE4.
- Analysis of diagnostic performance using receiver operating characteristic (ROC) curves and area under the curve (AUC) values.
Main Results:
- Both CEACAM6 and HE4 levels were significantly higher in MPE than in BPE across both cohorts.
- In the test cohort, CEACAM6 and HE4 showed AUCs of 0.862 and 0.826, respectively.
- The combination of CEACAM6 and HE4 achieved a superior AUC of 0.938 in the test cohort and 0.834 in the validation cohort, outperforming individual markers.
- The combination demonstrated good diagnostic efficacy (AUC = 0.800) in cytology-negative MPE cases.
- Adding CEA to the CEACAM6/HE4 combination further improved AUC to 0.819.
Conclusions:
- Pleural CEACAM6 and HE4 are effective biomarkers for differentiating MPE from BPE.
- The combined use of CEACAM6 and HE4 enhances diagnostic accuracy for MPE.
- This biomarker combination offers a valuable tool for MPE diagnosis, particularly in challenging cytology-negative effusions.
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