Histological specificity and diagnostic performance of a six-biomarker panel of lung cancer: An evaluation of a geographically-based multicenter study in China

Abstract Background: Lung cancer is the most common neoplasm among all cancers worldwide. Early diagnosis with minimal invasive procedures is ideal for lowering the patients’ burden and increasing survival rates. The value of serum tumor biomarkers used in lung cancer screening is still controversial in clinical practice.Methods: Serum levels of ProGRP, NSE, SCC-Ag, CEA, CYFRA21-1, and HE4 were measured using the chemiluminescence immunoassay in apparently healthy Chinese individuals, as well as in those with benign non-cancerous diseases, lung cancer patients, and those suffering other types of malignancies. Data was analyzed utilizing the SPSS version 18.0 statistical software. Results: All 6 serum biomarkers in lung cancers were significantly higher than in benign non-cancerous diseases and healthy controls. HE4 levels in benign diseases were significantly higher than in healthy controls. SCC-Ag, CEA, and CYFRA21-1 levels in lung cancers were significantly higher than in other malignancies. ProGRP and NSE levels in SCLC were significantly higher than in other histologic types; SCC-Ag and CYFRA21-1 levels in SCC were significantly higher than in other histologic types; the HE4 level in SCLC was also significantly higher than in SCC and adenocarcinoma, while adenocarcinoma had the highest serum CEA level comparing to SCC and SCLC. Serum ProGRP, NSE, and HE4 in SCLC were significantly higher than in NSCLC, SCC-Ag level in NSCLC was significantly higher than in SCLC. All biomarkers in advanced stages were significantly higher than in lower stages. NSE, HE4, and ProGRP presented relative high performance in SCLC. CYFRA21-1, HE4, and SCC-Ag indicated relative high performance in SCC. All biomarkers had relatively low performance on adenocarcinoma histologic type. The best performance of 2-marker combination was SCC-Ag+CYFRA21-1 for SCC, ProGRP+NSE for SCLC, CEA+CYFRA21-1 for adenocarcinoma. A combination of SCC+CEA+CYFRA21-1 gained highest performance for NSCLC.Conclusions: A 6-biomarker panel had capability on characterizing lung cancer and presented high performance individually and combinatorically on different histologic types of the neoplasm. HE4 showed high sensitivity to all histologic types of the malignancy; however, one should be cautious since its level also increased in benign non-cancerous diseases.