The investigation of levels of endothelial cell-specific molecule, progranuline, clusterin, and human epididymis protein 4 in the differential diagnosis of malignant pleural effusions

Abstract

Background: Progranulin (PGRN), endothelial cell-specific molecule-1, clusterin (CLU), and human epididymis protein 4 (HE-4) are novel proteins reported to have diagnostic and prognostic potential in lung cancer. Here, we aimed to identify the markers with high sensitivity and specificity in distinguishing malignant pleural fluids from other pleural fluids. Methods: This prospective, descriptive study was conducted at a medical faculty hospital between 2016 and 2019. The study population consisted of 90 patients <18 years of age with pleural effusion (PE). Levels of pleural fluids of PGRN, endothelial cell-specific molecule-1, CLU, and HE-4 were measured with enzyme-linked immunosorbent assay kits under the manufacturer’s manual. Results: Of 90 patients, 54 were men, and 36 were women (mean age 65 ± 16 years). Of pleural fluids investigated, 23 (25%) and 67 (74%) were transudates and exudates, respectively. Of exudates, while 27 (40%) and 19 (28%) were parapneumonic PE and tuberculous PE, respectively, 20 (29%) were malignant pleural effusion (MPE). Levels of all biomarkers in exudate fluids were found significantly higher than those of transudate fluids. CLU, HE-4, and PGRN levels in MPE were also found significantly higher than benign fluids ( P < .05). Cutoff values were achieved by receiver operating characteristics analysis for CLU, HE-4, and PGRN to distinguish between malignant and benign groups. For diagnosis of MPE, the sensitivity and specificity values were found as 0.66 and 0.67 for a cutoff value of CLU of 18.29 mg/L ( P = .00), as 0.76 and 0.76 for a cutoff value of HE-4 of 9.33 mg/L ( P = .00), and as 0.66 and 0.67 for a cutoff value of PGRN of 105.91 mg/L ( P = .001). Conclusion: HE-4 having high sensitivity and specificity can be a potential diagnostic marker in distinguishing between malignant and benign effusions, and these findings can constitute a basis for future research.

Value of human epididymis secretory protein 4 in differentiating malignant from benign pleural effusion: an analysis of two cohorts

“…First, previous studies only included lung cancer patients in MPE. 40,41 Our study found that the mean HE4 in lung cancer (1096 pmol/L) was higher than in other cancers (879 pmol/L). The difference in HE4 was marginally significant (p = 0.06), which may be due to the small sample size of our study.…”

“…HE4 has an AUC of approximately 0.75, lower than that reported in previous studies. [39][40][41] There are several possible explanations. First, previous studies only included lung cancer patients in MPE.…”

“…To our knowledge, three studies have evaluated the diagnostic accuracy of HE4 for MPE. [39][40][41] Compared with these studies, our study has some strengths. First, we investigated the diagnostic accuracy of HE4 with two independent cohorts (n = 210), and similar results were observed in both cohorts, indicating our findings were robust.…”

Diagnostic value of cerebrospinal fluid human epididymis protein 4 for leptomeningeal metastasis in lung adenocarcinoma

“…In lung cancer, serum HE4 can be used as the diagnosis biomarker for lung cancer (LC), particularly for early-stage LC ( 6 ), and correlates with poor prognosis, especially in Asian patients ( 7 ). HE4 in the pleural fluid can help differentiate malignant effusions from benign effusions ( 8 , 9 ). So far, research associated with HE4 in lung cancer has been mainly focused on serology and pleural effusion, few studies have investigated the clinical significance of HE4 in CSF.…”