Journal Article

Human epididymis protein 4, a novel potential biomarker for diagnostic and prognosis monitoring of lung cancer

Ye, Cuiping, Chu, Lanhe, Dong, Hangming, Zhang, Tingting, Tan, Wenchong

2024

Overview

Objective This study aimed to explore the application value of human epididymis protein 4 (HE4) in diagnosing and monitoring the prognosis of lung cancer. Methods First, TCGA (The Cancer Genome Atlas) databases were used to analyze whey‐acidic‐protein 4‐disulfide bond core domain 2 (WFDC2) gene expression levels in lung cancer tissues. Then, a total of 160 individuals were enrolled, categorized into three groups: the lung cancer group (n = 80), the benign lesions group (n = 40), and the healthy controls group (n = 40). Serum HE4 levels and other biomarkers were quantified using an electro‐chemiluminescent immunoassay. Additionally, the expression of HE4 in tissues was analyzed through immunohistochemistry (IHC). In vitro cultures of human airway epithelial (human bronchial epithelial [HBE]) cells and various lung cancer cell lines (SPC/PC9/A594/H520) were utilized to detect HE4 levels via western blot (WB). Results Analysis of the TCGA and UALCAN (The University of Alabama at Birmingham Cancer Data Analysis Portal) databases showed that WFDC2 gene expression levels were upregulated in lung cancer tissues (p < 0.01). Compared with the control group and the benign group, HE4 was significantly higher in the serum of patients with lung cancer (p < 0.001). Receiver operating characteristic (ROC) analysis confirmed that HE4 had better diagnostic efficacy than classical markers in the differential diagnosis of lung cancer and benign lesions and had the highest diagnostic value in lung adenocarcinoma (area under the ROC curve [AUC] = 0.826). HE4 increased in early lung cancer and positively correlated with poor prognosis (p < 0.001). Moreover, the results of WB and IHC revealed that the expression of HE4 was increased in lung cancer cells (SPC/A549/H520) and lung cancer tissues but decreased in PC9 cells with a lack of exon EGFR19 (p < 0.05). Conclusion Serum HE4 emerges as a promising novel biomarker for the diagnosis and prognosis assessment of lung cancer. Our study first used large public databases to analyze the expression of the WFDC2 gene in lung cancer tissues and then compared HE4 with classical tumor markers at the serological level. Finally, western blot and immunohistochemistry were used to detect the expression characteristics of HE4 in lung cancer cells and tissues. Our results show that serum HE4 emerges as a promising novel biomarker for the diagnosis and prognosis assessment of lung cancer.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc,Wiley
• Subject: Aged / Biomarkers / Biomarkers, Tumor - blood / Biomarkers, Tumor - genetics / Biomarkers, Tumor - metabolism / Cell Line, Tumor / diagnosis / Female / Gene expression / Gene Expression Regulation, Neoplastic / human epididymis protein 4 / Humans / Immunohistochemistry / lung adenocarcinoma / Lung cancer / Lung Neoplasms - diagnosis / Lung Neoplasms - genetics / Lung Neoplasms - metabolism / Lung Neoplasms - pathology / Male / Middle Aged / Original / Prognosis / Proteins / WAP Four-Disulfide Core Domain Protein 2 - analysis / WAP Four-Disulfide Core Domain Protein 2 - metabolism