The Changes Of VEGF Levels And Functions Of CD4~+T Cells In Peripheral Blood Of Obstructive Sleep Apnea-Hypopnea Syndrome Patients Complicated With Lung Cancer

Background:Studies have confirmed that obstructive sleep apnea hypopnea syndrom(OSAHS)increased incidence and mortality of tumor.At present,a lot of researches about OSAHS and tumor focused on the animal experiments,but researches about the relationship between OSAHS and occurrence and development of tumor as well as immune regulation in the human body are still rare.Objective:To explore the mechanisms how OSAHS promote progression of lung cancer,we detect circulating VEGF levels and immunological functions of CD4+T cells of OSAHS patients and patients complicated with lung cancer.Methods:According to inclusion criteria,17 cases of control group,15 cases of mild-to-moderate OSAHS group,15 cases of severe OSAHS group were recruited from 2017.01 to 2018.01 in Guangdong General Hospital,and were compared corresponding index changes of OSAHS patients of different severities.At the same time we recruited 22 cases of OSAHS group,27 cases of lung cancer group,22 cases of OSAHS complicated with lung cancer group according to inclusion criteria,compared differences between immune indexes and VEGF of OSAHS patients whether complicated with lung cancer or not.We analyzed the correlation of immune indexes and the differences between various indicators according to tumor TNM stages in OSAHS complicated with lung cancer group.All objects were detected by PSG,informations about hypoxia degree at night were collected.Venous blood of each object was collected.CTLA-4 and PD-1 expression levels on Foxp3+Treg cells and CD4+ T cell in peripheral blood samples were assayed by fluorescence-activated cell sorter(FACS),the concentration of circulating TGF-?1,VEGF,IL-10 levers were detected by ELISA.SPSS 22.0 software was used to statistically analyze.Results:1.VEGF?TGF-?1?IL-10 and functions of CD4+T cells and Tregs of OSAHS patients:Compared with the control group,VEGF concentration in severe OSAHS group was significantly higher(P<0.05).TGF-?1 concentration in mild-to-moderate OSAHS group and severe OSAHS group was significantly higher than that of control group(P<0.05).IL-10 levels,CD4+T cells and Foxp3+Treg proportion and inhibitory molecules CTLA-4,PD-1 expression were not significantly different between the control group,mild-to-moderate OSAHS group and severe OSAHS group(P>0.05).VEGF concentration was negatively correlated with the lowest SpO2,and positively correlated with AHI,ODI and proportion of SpO2 less than 90%.2.VEGF?TGF-?1?IL-10 and functions of CD4+T cells and Tregs of OSAHS patients complicated with lung cancer:VEGF and TGF-?1 concentration in OSAHS complicated with lung cancer group were significantly higher than that in OSAHS group and lung cancer group(P<0.05).VEGF?IL-10 and TGF-?1 concentration in lung cancer group were significantly higher than that in OSAHS group(P<0.05).CD4+T cell proportion,CTLA-4+CD4+T cell proportion,PD-l+CD4+T cell proportion were not significantly different between OSAHS group,lung cancer group and OSAHS complicated with lung cancer group(P>0.05).Foxp3+Treg cells ratio,Foxp3 average fluorescence intensity of Treg cells and CTLA-4+CD4+T cell ratios in OSAHS complicated with lung cancer group and lung cancer group were significantly higher than that in OSAHS group(P<0.01).Foxp3+Treg cells ratio,Foxp3 average fluorescence intensity of Treg cells and CTLA-4+Foxp3+Treg ratio in OSAHS complicated with lung cancer group were significantly higher than that in lung cancer group(P<0.05).3.Changes of immune indexes in different TMN stages of OSAHS complicated with lung cancer group:IL-10 TGF-?1?Foxp3+Treg ratio and CTLA-4+Foxp3+Treg ratio showed a tendency of increase with TMN stages,but there was no significant difference.VEGF concentration in stage ? was significantly higher than that was in stage ?-?and stage ?(P<0.05).Foxp3 average fluorescence in stage IV and stage ? was significantly higher than that in stage ?-?(P<0.05).The ratio of CD4+T cells in stage IV was significantly lower than that in stage ?-? and stage ?(P<0.05).4.The correlation between immune indexes and hypoxia degree at night in OSAHS complicated with lung cancer group:CD4+T cells ratio was negatively correlated with proportion of SpO2 lower than 90%and was positively correlated with the lowest SpO2.CTLA-4+CD4+T cell ratio and CTLA-4+Foxp3+ Tregs were negatively correlated with the lowest SpO2(P<0.05).There was no correlation between Foxp3+Tregs?Foxp3 average fluorescence?PD-1+CD4+T cells?VEGF concentration?IL-10 concentration?TGF-?1 concentration and AHI?ODI?proportion of SpO2 less than 90%?the lowest SpO2(P>0.05).5.The correlation between immune indexes in OSAHS complicated with lung cancer group:CD4+T cells ratio was negatively correlated with Foxp3+ Tregs and Foxp3 average fluorescence intensity of Treg cells.There was no correlation between CTLA-4+CD4+T cell ratio?CTLA-4+Foxp3+Tregs?CD4+T cells ratio?PD-1+CD4+T cell ratio and IL-10?VEGF?TGF-?1(P>0.05).Conclusion:1.The expression of VEGF and TGF-?1 of OSAHS patients up-regulated,and the expression of VEGF increased with the serious degree of OSAHS,which reveal that imbalanced expression of inflammatory factors and anti-inflammatory factors may play an important role in the occurrence mechanism of OSAHS.2.The expression of VEGF and TGF-?1 in peripheral blood of obstructive sleep apnea-hypopnea syndrome patients complicated with lung cancer significantly up-regulated,at the same time,functions of Tregs and expression of co-inhibitory molecular CTLA-4 on CD4+ T cells up-regulated,which indicated that VEGF?Tregs and CD4+T cells may involve in the occurrence and development of pulmonary cancer.3.The expression of VEGF increased and the number of CD4+ T cells decreased in patients with terminal lung cancer.