Early diagnosis and histological subtyping are important issues in the management of patients with lung cancer (LC). The aim of this study is to investigate the diagnostic value of a panel of serum tumor markers in newly diagnosed patients with LC.

Venous blood samples were collected from 99 patients with LC (42 adenocarcinoma, 35 squamous, and 22 small cell carcinoma) and 30 patients with benign lung disease. Progastrin releasing peptide (ProGRP), squamous cell carcinoma antigen (SCCAg), cytokeratin 19-fragments (CYFRA 21.1), human epididymis protein 4 (HE4), Chromogranin A (CgA) and neuron specific enolase (NSE) levels were measured. The diagnostic value of the biomarkers was assessed with ROC curve analyses; the area under the curve (AUC) was calculated.

Serum CYFRA 21.1, ProGRP, SCCAg, NSE levels were significantly higher in LC patients. While ProGRP levels were higher (p = 0.009) in SCLC; CYFRA 21.1 and SCCAg levels were higher in NSCLC (p = 0.019 and p = 0.001, respectively). The sensitivity and specificity of tumor markers were 72%, 83% for CYFRA 21.1; 70%, 57% for HE4; 18%, 93% for ProGRP; 43%, 77% for SCCAg; 54%, 53% for CgA; 73%, 50% for NSE. CYFRA 21.1 (p < 0.001, r = 0.394), HE4 (p = 0.014, r = 0.279) and CgA (p = 0.023, r = 0.259) levels were positively correlated with tumor stage in NSCLC. CgA levels were significantly higher in extensive stage SCLC (p = 0.004). CYFRA 21.1 had the highest diagnostic value for LC (AUC = 0.865). When it is combined with HE4, diagnostic value increased (AUC = 0.899). ProGRP had the highest diagnostic value (AUC = 0.875, p < 0.001) for discriminating SCLC from NSCLC.

A panel of three tumor markers CYFRA 21.1, HE4 and ProGRP may play a role for discriminating LC from benign lung disease and subtyping as SCLC.