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

Abstract

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.

A glycolysis-based three-gene signature predicts survival in patients with lung squamous cell carcinoma

“…This phenomenon is a unique energy metabolism that exists in cancer cells. In recent years, many biomarkers for LUSC have been discovered, including glycolysis-associated genes such as kininogen 1 (KNG1) [ 8 ] and tripartite motif-containing protein 59 (TRIM59) [ 9 ].…”

A glycolysis-based three-gene signature predicts survival in patients with lung squamous cell carcinoma

“…7 This phenomenon is a unique energy metabolism exist in cancer cells. In recent years, many biomarkers, including glycolysis-associated genes, for LUSC have been determined, such as kininogen 1 (KNG1) 8 and tripartite motif-containing protein 59 (TRIM59). 9 With the development of high-throughput sequencing, various patient genome databases were constructed, which makes us have a deep understanding of genomic changes.…”

Urinary Biomarkers for Early Diagnosis of Lung Cancer

“…In 2015, Mazzone [33] analyzed the volatile organic compounds (VOCs) of the urinary headspace, finding a signature that could distinguish lung cancer patients utilizing a colorimetric sensor array exposed to the headspace gas of neat and pre-treated urine can-cerous samples. Other studies [34][35][36][37] used immunosorbent assays, such as enzyme-linked immunosorbent assay (ELISA).…”