The Evaluation of Urinary HE4, CEA, ProGRP, CYFRA 21-1 and NSE in the Diagnosis of Lung Cancer.

Objective: Urinary proteins are effective tumor biomarkers. Human epididymis protein 4 (HE4), progastrin-releasing peptide (ProGRP), carcinoembryonic antigen (CEA), cytokeratin-19 fragment 21-1(CYFRA 21-1), and neuron-specific enolase (NSE) in serum, were proposed as tumor biomarkers of lung cancer. Our aim was to identify the urine protein biomarkers that can distinguish patients with lung cancer from healthy individuals and/or patients with benign lung disease with a high level of sensitivity and specificity.

Methods: These urinary protein concentrations were determined from 212 patients with lung cancer, 80 patients with benign pulmonary conditions, and 100 healthy individuals.

Results: In the lung cancer group, urine HE4 median concentration was approximately ten times that in the healthy and/or pulmonary benign disease group; urine CEA, CYFRA21-1, and NSE median concentrations were about eight times, twice, and half as those in the healthy group, respectively. However, the median concentrations of urine ProGRP were almost the same in the healthy, lung benign, and cancer groups. Urine HE4 showed better specificity (94.0% vs 86.0%) and sensibility (72.38% vs 60.65%) than CEA in discriminating patients with lung cancer from healthy controls. A significantly higher ROC area was also obtained with urine HE4 than with CEA (0.87 vs 0.76).

Conclusions: Urine HE4 showed the best diagnostic performance, followed by CEA. The levels of urine HE4 and CEA increased significantly in patients with lung cancer, which had little relationship with pathological type and metastasis.