Evaluation of kininogen 1, osteopontin and α-1-antitrypsin in plasma, bronchoalveolar lavage fluid and urine for lung squamous cell carcinoma diagnosis

Lung squamous cell carcinoma (LUSC) progression is accompanied by changes in protein levels that may be reflected in body fluids, such as plasma, bronchoalveolar lavage fluid (BALF) and urine. Certain proteins present in these biofluids can facilitate lung cancer diagnosis. Kininogen 1 (KNG1), osteopontin (OPN) and α-1-antitrypsin (AAT) are associated with tumorigenesis. The present study aimed to explore the combined monitoring of plasma, urine and BALF to gain insight into LUSC by monitoring the levels of the above three protein using ELISA. LUSC (n=31) and healthy controls with benign lung diseases (n=20) were enrolled in the study. KNG1 levels in plasma, BALF and urine were significantly higher in patients with LUSC patients than in controls (P<0.0001, P<0.0001 and P=0.0010, respectively). OPN was upregulated in the plasma and BALF of patients with LUSC relative to controls (P=0.0107 and P=0.0004, respectively), whereas its levels in the urine of healthy controls were significantly higher (P=0.0088). Patients with LUSC had higher AAT levels in plasma, BALF and urine compared with those of the controls (P=0.0022, P=0.0014 and P=0.0005, respectively). Receiver operating characteristic analysis showed an area under the curve (AUC) of 0.81 for KNG1 in plasma, 0.91 in BALF and 0.81 in urine. The AUC for OPN was 0.71 in plasma, 0.83 in BALF and 0.75 in urine. The AUC for AAT was 0.74 in plasma, 0.74 in BALF and 0.86 in urine. Immunohistochemical staining in 20 paired LUSC and adjacent normal tissues showed that KNG1, OPN and AAT levels were higher in LUSC tissues. Therefore, our results showed that KNG1, OPN and AAT in biofluids might be useful for the diagnosis of LUSC. These markers in urine and BALF may be better than in plasma for detecting LUSC.