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 10 publications

(12 citation statements)

References 17 publications

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“…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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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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“…Homozygous WFDC2 deletion mice showed increased apoptosis of type-I alveolar cells in lung tissues [ 24 ] and suffered severe dyspnea. WFDC2 protein is elevated in malignant pleural effusion and has diagnostic value in LUAD, squamous cell carcinoma, and small cell carcinoma [ 25 ]. Our results showed elevated levels of WFDC2 in the plasma of early-stage LUAD patients and enhanced proliferation of lung cancer cells with ectopic expression of WFDC2.…”

Section: Discussionmentioning

confidence: 99%

Secreted proteins MDK, WFDC2, and CXCL14 as candidate biomarkers for early diagnosis of lung adenocarcinoma

Hao

et al. 2023

BMC Cancer

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Background Early diagnosis of lung adenocarcinoma (LUAD), one of the most common types of lung cancer, is very important to improve the prognosis of patients. The current methods can’t meet the requirements of early diagnosis. There is a pressing need to identify novel diagnostic biomarkers. Secretory proteins are the richest source for biomarker research. This study aimed to identify candidate secretory protein biomarkers for early diagnosis of LUAD by integrated bioinformatics analysis and clinical validation. Methods Differentially expressed genes (DEGs) of GSE31210, gene expression data of early stage of LUAD, were analyzed by GEO2R. Upregulated DEGs predicted to encode secreted proteins were obtained by taking the intersection of the DEGs list with the list of genes encoding secreted proteins predicted by the majority decision-based method (MDSEC). The expressions of the identified secreted proteins in the lung tissues of early-stage LUAD patients were further compared with the healthy control group in mRNA and protein levels by using the UALCAN database (TCGA and CPTAC). The selected proteins expressed in plasma were further validated by using Luminex technology. The diagnostic value of the screened proteins was evaluated by receiver operating characteristic (ROC) analysis. Cell counting kit-8 assay was carried out to investigate the proliferative effects of these screened proteins. Results A total of 2183 DEGs, including 1240 downregulated genes and 943 upregulated genes, were identified in the GSE31210. Of the upregulated genes, 199 genes were predicted to encode secreted proteins. After analysis using the UALCAN database, 16 molecules were selected for further clinical validation. Plasma concentrations of three proteins, Midkine (MDK), WAP four-disulfide core domain 2 (WFDC2), and C-X-C motif chemokine ligand 14 (CXCL14), were significantly higher in LUAD patients than in healthy donors. The area under the curve values was 0.944, 0.881, and 0.809 for MDK, WFDC2, and CXCL14, 0.962 when combined them. Overexpression of the three proteins enhanced the proliferation activity of A549 cells. Conclusions MDK, WFDC2, and CXCL14 were identified as candidate diagnostic biomarkers for early-stage LUAD and might also play vital roles in tumorigenesis.

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

Cited by 10 publications

References 17 publications

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

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

Secreted proteins MDK, WFDC2, and CXCL14 as candidate biomarkers for early diagnosis of lung adenocarcinoma

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