Correlation Between Clinicopathological Characteristics And EGLN1 Expression In Patients With Lung Adenocarcinoma And OSA

Objectives:To explore the clinical and pathological characteristics of lung adenocarcinoma patients with different severity of obstructive sleep apnea and their correlation with sleep breathing monitoring indicators;to analyze the expression of Egl-9 family hypoxia inducible factor 1（EGLN1）in lung adenocarcinoma and its correlation with sleep breathing monitoring indicators.Methods:The differentially expressed genes in cancerous and paracancerous tissues of 4 patients with lung adenocarcinoma and OSA were detected by gene sequencing to search for target genes.From January 1,2021 to Decem-ber 30,2022,51 patients with lung adenocarcinoma who were admitted to the thoracic surgery department of the Second Affiliated Hospital of Kunming Medical University due to lung occupying lesions and needed surgery or lung puncture were selected.The patients were monitored for nocturnal Polysomnography（PSG）before surgery or puncture,and the cancerous and paracancerous of patients with lung adenocarcinoma were collected after surgery and pathological results were obtained.Collect the general data,sleep breathing monitoring indicators and clinicopathological parameters of lung adenocarcinoma of these patients.According to the apnea hyponea index（AHI）value of the patients,they were divided into three groups:simple lung adenocarcinoma group（17 cases）,lung adenocarcinoma combined with mild OSA group（19 cases）,and lung adenocarcinoma with moderate and severe OSA group（15 cases）.The m RNA expression of the target gene EGLN1 in the tissues was detected by q-PCR experiment.Westernblot test verified the expression level of EGLN1 protein in tissues.To analyze whether there are differences in clinicopathological parameters,EGLN1 gene m RNA expression,and EGLN1 protein expression levels in patients with lung adenocarcinoma patients with OSA of different severity,and their correlation with sleep breathing monitoring indicators.Further,the GEPIA database was used to analyze and verify the expression of EGLN1 in lung adenocarcinoma,and the Kaplan-Meier Plotter database was used to analyze and verify the impact of EGLN1 gene m RNA expression on the overall survival period of lung adenocarcinoma patients.Results:1.Through gene sequencing,a total of 442 significantly differential genes were screened from the cancerous and paracancerous tissues of 4 patients with lung adenocarcinoma and OSA.The hypoxia related gene EGLN1 was located in the upregulated 64 genes,and EGLN1 was ultimately selected as the target gene of this research.2.The proportion of male patients with lung adenocarcinoma combined with moderate and severe OSA group was significantly higher than that in the simple lung adenocarcinoma group and the lung adenocarcinoma combined with mild OSA group（P<0.05）.The proportion of male patients in the lung adenocarcinoma combined with mild OSA group was significantly higher than that in the simple adenocarcinoma group（P<0.05）.The age of lung adenocarcinoma with mild OSA and lung adenocarcinoma with moderate and severe OSA was significantly higher than that of simple lung adenocarcinoma group（P<0.05）.There was no statistically significant difference in BMI,smoking and drinking history among the three groups（P>0.05）;The AHI and oxygen reduction index（ODI）in the lung adenocarcinoma combined with moderate and severe OSA group were significantly higher than those in the lung adenocarcinoma combined with mild OSA group and simple lung adenocarcinoma group（P<0.05）,and the AHI and ODI in the lung adenocarcinoma combined with mild OSA group were significantly higher than those in the simple lung adenocarcinoma group（P<0.05）.The mean apnea duration（MAD）,and the longest apnea duration（LAD）of lung adenocarcinoma combined with mild OSA and lung adenocarcinoma combined with moderate and severe OSA were significantly higher than those of simple lung adenocarcinoma group（P<0.05）,and lowest pulse oxygen saturation（LSPO₂）were significantly lower than those of simple lung adenocarcinoma group（P<0.05）.The LHD of lung adenocarcinoma combined with moderate and severe OSA was significantly higher than those of lung adenocarcinoma combined with mild OSA group and simple lung adenocarcinoma group.There was no significant difference in average pulse oxygen saturation（Avg SPO₂）among the three groups（P>0.05）;The lung adenocarcinoma combined with moderate and severe OSA group had higher TNM staging than the simple lung adenocarcinoma group and the lung adenocarcinoma combined with mild OSA group（P<0.05）.The tumor diameter of lung adenocarcinoma with mild OSA and lung adenocarcinoma with moderate and severe OSA group was hinger than that of simple lung adenocarcinoma group（P<0.05）.The percentage of tumor cells expressing Ki-67 in lung adenocarcinoma combined with moderate and severe OSA group was higher than that in simple lung adenocarcinoma group（P<0.05）.There was no significant difference between the three groups in whether there was distant metastasis,lymph node metastasis and T stage（P>0.05）.The tumor TNM staging was positively correlated with AHI,ODI,MAD,LAD,LDH（r=0.446,r=0.428,r=0.457,r=0.446,r=0.293;all P<0.05）,and negatively correlated with LSPO₂（r=-0.379,P<0.05）.The tumor diameter was positively correlated with AHI,ODI,MAD,LDH（r=0.504,r=0.316,r=0.314,r=0.294;all P<0.05）,but not with LSPO₂（P>0.05）.The percentage of tumor cells expressing Ki-67 was positively correlated with AHI（r=0.382,P<0.05）,but not with ODI,MAD,LDH and LSPO2（P>0.05）.3.The m RNA expression of EGLN1 gene in lung adenocarcinoma tissue was significantly higher than that in adjacent tissues（P<0.05）.The expression of EGLN1gene m RNA in lung adenocarcinoma patients with moderate and severe OSA was significantly higher than that in simple lung adenocarcinoma patients（P<0.05）.The m RNA expression of EGLN1 gene in lung adenocarcinoma was positively correlated with AHI（r=0.917,P<0.05）,but not with ODI,MAD,LAD,LHD and LSPO₂（P>0.05）.4.The expression level of EGLN1 protein in lung adenocarcinoma tissue was significantly higher than higher than that in adjacent tissues（P<0.05）.The expression level of EGLN1 protein in lung adenocarcinoma patients with moderate and severe OSA was significantly higher than that in simple lung adenocarcinoma patients and the lung adenocarcinoma combined with mild OSA group（P<0.05）.The relative expression level of EGLN1 protein in lung adenocarcinoma was positively correlated with AHI、ODI and LAD（r=0.671,r=0.666,r=0.691;all P<0.05）,and negatively correlated with LSPO₂（r=-0.582,P<0.05）,but not with MAD and LHD（P>0.05）.5.Through Gene Expression Profiling Interactive Analysis（GEPIA）database,it was found that the gene expression of EGLN1 in tumor tissue of lung adenocarcinoma patients and their matched normal tissue was different,and the median expression of EGLN1 in tumor tissue was higher than that in normal lung tissue.Draw the survival curve of lung adenocarcinoma patients with high and low expression of EGLN1 gene m RNA through Kaplan-Meier Plotter database.It was found that the OS of those with high expression of EGLN1 gene was significantly lower than those with low expression of EGLN1 gene（P<0.05）.Conclusions:1.The expression level of EGLN1 in lung adenocarcinoma is higher than that in normal lung tissue.2.The expression level of EGLN1 is positively correlated with AHI and negatively correlated with LSPO₂.The higher the severity of OSA,the higher the expression level of EGLN1.3.The overall survival period of OSA patients with high expression of EGLN1 is significantly reduced.