Serum Human Epididymis Secretory Protein 4 (HE4) is a Potential Prognostic Biomarker in Non-Small Cell Lung Cancer.

Background: Human epididymis secretory protein 4 (HE4) is a secreted glycosylated protein belonging to the WFDC family, which is an ideal biomarker in ovarian cancer. However, the role of HE4 in lung cancer is still unclear. The study aimed to evaluate serum levels of HE4 as a prognostic biomarker in patients with non-small cell lung cancer (NSCLC).

Methods: The subjects consisted of 217 NSCLC patients, which were compared to a control group of 80 patients with benign lung disease and 110 healthy controls. Serum levels of HE4 were measured with electrochemiluminescence assays in a Roche E601 Immunoassay Analyzer.

Results: Serum levels of HE4 in NSCLC patients were significantly higher than in benign lung disease and healthy controls (p < 0.001). Using the cutoff value of 78.84 pmol/L, HE4 levels differentiated NSCLC from healthy controls with a sensitivity of 84.2% and a specificity of 78.3%. In the NSCLC subgroups, HE4 was a better discriminator of lung adenocarcinoma (cutoff value, 72.70 pmol/L, area under curve, 0.909; 95% confidence interval, 0.871 - 0.947). Higher serum HE4 levels were significantly correlated with histological type, high TNM stage, and positive lymph node metastasis (p = 0.019, 0.018, 0.002, respectively). Kaplan-Meier analysis demonstrated that high HE4 levels predicted poor survival (log-rank test: p = 0.007), especially in the adenocarcinoma group (logrank test: p = 0.001). In the Cox model, serum HE4 level was an independent prognostic factor for NSCLC.

Conclusions: Higher serum levels of HE4 predict poor prognosis in NSCLC patients, especially in patients with adenocarcinoma.