Diagnostic value of human epididymis protein 4 in malignant pleural effusion in lung cancer

Lv, Min; Wang, Fen; Wang, Xiaoyan; Zhang, Cuilan

doi:10.3233/cbm-190840

Cited by 9 publications

(12 citation statements)

References 17 publications

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“…Human epididymis protein 4 (HE4) has been for long considered a specific ovarian cancer biomarker, though a recent metaanalysis emphasized its moderate diagnostic accuracy for lung cancer (14). To date, two studies have investigated the diagnostic accuracy of HE4 for MPE (15,16). In the first, the authors prospectively enrolled 32 patients with MPE and 54 patients with benign pleural effusion (BPE).…”

Section: Conventional Cancer Biomarkersmentioning

confidence: 99%

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Pleural biomarkers in diagnostics of malignant pleural effusion: a narrative review

Zhang¹,

Li²,

Lippi³

et al. 2021

Transl Lung Cancer Res

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Although cytology and pleural biopsy of pleural effusion (PE) are the gold standards for diagnosing malignant pleural effusion (MPE), these tools' diagnostic accuracy is plagued by some limitations such as low sensitivity, considerable inter-observer variation and invasiveness. The assessment of PE biomarkers may hence be seen as an objective and non-invasive diagnostic alternative in MPE diagnostics. In this review, we summarize the characteristics and diagnostic accuracy of available PE biomarkers, including carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), carbohydrate antigens 125 (CA125), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 15-3 (CA15-3), a fragment of cytokeratin 19 (CYFRA 21-1), chitinase-like proteins (CLPs), vascular endothelial growth factor (VEGF) and its soluble receptor, endostatin, calprotectin, cancer ratio, homocysteine, apolipoprotein E (Apo-E), B7 family members, matrix metalloproteinase (MMPs) and tissue-specific inhibitors of metalloproteinases (TIMPs), reactive oxygen species modulator 1 (Romo1), tumor-associated macrophages (TAMs) and monocytes, epigenetic markers (e.g., cell-free microRNA and mRNA). We summarized the evidence from systematic review and meta-analysis for traditional tumor markers' diagnostic accuracy. According to the currently available evidence, we conclude that the traditional tumor markers have high specificity (around 0.90) but low sensitivity (around 0.50). The diagnostic accuracy of novel tumor markers needs to be validated by further studies. None of these tumor biomarkers would have sufficient diagnostic accuracy to confirm or exclude MPE when used alone. A multi-biomarker strategy, also encompassing the use of artificial intelligence algorithms, may be a valuable perspective for improving the diagnostic accuracy of MPE.

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Section: Conventional Cancer Biomarkersmentioning

confidence: 99%

“…In the second study, the authors investigated the diagnostic accuracy of HE4 for lung cancer-associated MPE (15) and found that pleural HE4 had an AUC of 0.83 for diagnosing MPE. At the 652.2 pmol/L threshold, the sensitivity and specificity of HE4 were 0.78 and 0.75, respectively.…”

Section: Conventional Cancer Biomarkersmentioning

confidence: 99%

Pleural biomarkers in diagnostics of malignant pleural effusion: a narrative review

Zhang¹,

Li²,

Lippi³

et al. 2021

Transl Lung Cancer Res

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show abstract

“…Elevation of HE4 in serum and pleural effusion were found in NSCLS patients, making it a potential new lung cancer biomarker. 13,14 To date, the sensitivity and specificity of lung cancer biomarkers are still a bottleneck to overcome in lung cancer screening and diagnosis. There is thus an urgent need to improve lung cancer risk assessments because current in vitro diagnosis-based screening criteria miss a large number of cases.…”

Section: Introductionmentioning

confidence: 99%

Age‐stratified and gender‐specific reference intervals of six tumor markers panel of lung cancer: A geographic‐based multicenter study in China

Zhang

et al. 2021

Clinical Laboratory Analysis

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“…Additionally, patients with lung adenocarcinoma demonstrated significantly higher levels of HE-4 than those with squamous cell carcinoma and small cell carcinoma. [ 27 ] In another study conducted in 88 patients with different types of PE by Elsammak et al, both serum HE-4 levels and HE-4 levels of PE were detected to be significantly higher in the patients with lung and extrapulmonary malignant effusions than those with transudative or nonmalignant exudative effusion. In the study, a cutoff value of 1.675 pmol/L was revealed in pleural fluid with a diagnostic sensitivity of 85.3% and a specificity of 90.7%, predicting malignant PEs.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2022

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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.

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Diagnostic value of human epididymis protein 4 in malignant pleural effusion in lung cancer

Cited by 9 publications

References 17 publications

Pleural biomarkers in diagnostics of malignant pleural effusion: a narrative review

Pleural biomarkers in diagnostics of malignant pleural effusion: a narrative review

Age‐stratified and gender‐specific reference intervals of six tumor markers panel of lung cancer: A geographic‐based multicenter study in China

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

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