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.

Annals of Medicine
|April 15, 2025
PubMed
Abstract

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.