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

睡眠呼吸暂停会增加高危患者和已确诊肺癌患者的免疫逃逸、淋巴管生成和肿瘤细胞侵袭性的生物标志物。

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作者:Carolina Cubillos-Zapata ,Fernanda Troncoso-Acevedo ,Elena Díaz-García ,Enrique Alfaro ,Carolina Gotera-Rivera ,Teresa Pérez-Warnisher ,Germán Peces-Barba ,Luis M Seijo ,Francisco García-Río

Abstract

Background: Intermittent hypoxaemia 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. Methods: 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. Soluble levels of programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1), cytotoxic T-lymphocyte antigen-4, midkine (MDK), paraspeckle component-1 (PSPC1), transforming growth factor-β1 (TGF-β1), SMAD3, matrix metalloproteinase-2 and co-stimulus receptor of the tumour necrosis factor family of receptors (CD137) were determined by ELISA. Results: The presence of moderate-to-severe OSA was associated with increased levels of PSPC1, MDK, PD-L1 and PD-1 in screened individuals, and with higher values of PSPC1, TGF-β1, PD-L1 and PD-1 in patients with established lung cancer. The findings correlated with nocturnal intermittent hypoxaemia indices. 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.

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