Sleep apnoea increases biomarkers of immune evasion, lymphangiogenesis and tumour cell aggressiveness in high-risk patients and those with established lung cancer

Abstract

Intermittent hypoxemia and obstructive sleep apnoea (OSA) have been linked to lung cancer through as yet unidentified pathophysiological mechanisms. This study evaluates the effect of OSA on serum levels of biomarkers of immunosurveillance, lymphangiogenesis, and intrinsic tumour cell aggressiveness in high-risk individuals screened for lung cancer and patients with established lung cancer.Serum samples from individuals participating in a lung cancer screening cohort (SAILS study) or with newly diagnosed lung cancer (SAIL study) were analysed. All patients underwent home sleep apnoea testing (HSAT). Soluble levels of program death-1 (PD-1), program death ligand-1 (PD-L1), cytotoxic T-lymphocyte antigen 4 (CTLA4), midkine (MDK), paraspeckle protein-1 (PSPC-1), transforming growth factor-β1 (TGF-ß1), SMAD3, matrix metalloproteinase-2 (MMP2) and co-stimulus receptor of the tumour necrosis factor family of receptors (CD137) were determined by EIA.The presence of moderate-severe OSA was associated with increased levels of PSPC-1, MDK, PD-L1 and PD-1 in screened individuals, and with higher values of PSPC-1, TGF-ß1, PD-L1 and PD-1 in patients with established lung cancer. The findings correlated with nocturnal intermittent hypoxemia indices.In conclusion, moderate to severe OSA is associated with increased expression of serum biomarkers of immune evasion, lymphangiogenesis and tumour cell aggressiveness in high-risk individuals screened for lung cancer and those with established disease.

A review of obstructive sleep apnea and lung cancer: epidemiology, pathogenesis, and therapeutic options

“…Lymphangiogenesis, in addition to angiogenesis, mediates tumor vascularization, which meets the oxygen and nutrient requirements for tumor growth and metastasis ( 84 ). Recent studies have shown that individuals at high risk for lung cancer with moderate-to-severe OSA have elevated expression of MDK (non-OSA: 1536 pg/mL, 95% CI 840–2360 pg/mL; moderate-to-severe OSA: 5902 pg/mL, 95% CI 816–8337 pg/mL) ( 85 ).…”

Linking obstructive sleep apnoea and lung cancer: a further step down the road

“…In the current issue of ERJ Open Research , C ubillos- Z apata et al [ 10 ] add new evidence of other possible pathophysiological pathways to explain the association of OSA with lung cancer, in this case represented by various biomarkers of immune evasion (programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1)), lymphangiogenesis (midkine (MDK)) and intrinsic tumour cell aggressiveness (paraspeckle component-1 (PSPC1) and transforming growth factor (TGF)-β1), whose expression is shown to increase in the present study in both patients with moderate–severe OSA with established lung cancer and individuals with a high risk of suffering from lung cancer participating in a screening programme.…”