Serum β-klotho is a potential biomarker in the prediction of clinical outcomes among patients with NSCLC

J Thorac Dis. 2021 May;13(5):3137-3150. doi: 10.21037/jtd-21-798.

Abstract

Background: We aimed to investigate the β-klotho (KLB) expression in non-small cell lung cancer (NSCLC) and to determine its value as a novel molecular target for survival prognosis in patients with NSCLC.

Methods: The serum KLB concentrations in 50 patients with NSCLC and the 20 healthy persons were measured by enzyme-linked immunosorbent assay (ELISA) methods. The relationship between serum KLB level, including the level change after therapy, and the progression-free survival (PFS) and overall survival (OS) were analyzed. The KLB expression in A549 cells was measured by real-time polymerase chain reaction (RT-PCR) and western blotting. The function of cells was revealed by in vitro studies.

Results: The concentrations of serum KLB in patients with NSCLC were obviously lower than those in healthy subjects. KLB expression was significantly increased in patients after chemotherapy and epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) targeted therapy. In addition, expression of KLB was positively related with PFS and OS. Compared with 16-human bronchial epithelial (HBE) cells, the expression level of KLB was significantly decreased in A549 cells. Overexpression of KLB suppressed the proliferation of A549 cells, along with G1-to-S phase arrest and apoptosis induction.

Conclusions: KLB plays an anti-tumorigenic role in NSCLC. KLB may be a candidate target for the diagnosis and treatment of NSCLC and may serve a potentially significant role in future clinical applications.

Keywords: Non-small cell lung cancer (NSCLC); overall survival (OS); progression-free survival (PFS); survival prognosis; β-klotho (KLB).