Abstract
Based on our hospital database, the incidence of lung cancer diagnoses was similar in obstructive sleep apnea Syndrome (OSAS) and hospital general population; among individual with a diagnosis of lung cancer, the presence of OSAS was associated with an increased risk for mortality. In the gene expression and network-level information, we revealed significant alterations of molecules related to HIF1 and metabolic pathways in the hypoxic-conditioned lung cancer cells. We also observed that GBE1 and HK2 are downstream of HIF1 pathway important in hypoxia-conditioned lung cancer cell. Furthermore, we used publicly available datasets to validate that the late-stage lung adenocarcinoma patients showed higher expression HK2 and GBE1 than early-stage ones. In terms of prognostic features, a survival analysis revealed that the high GBE1 and HK2 expression group exhibited poorer survival in lung adenocarcinoma patients. By analyzing and integrating multiple datasets, we identify molecular convergence between hypoxia and lung cancer that reflects their clinical profiles and reveals molecular pathways involved in hypoxic-induced lung cancer progression. In conclusion, we show that OSAS severity appears to increase the risk of lung cancer mortality.
Highlights
Epidemiological evidence has suggested that obstructive sleep apnea Syndrome (OSAS) is associated with a higher prevalence of cancer and cancer-related mortality; laboratory-based observations have revealed that constitutive components of OSAS are mechanistically involved in accelerated tumor growth and progression
Data based on hospital population: OSAS severity was associated with clinical parameters and overall survival in patients with lung cancer
Our work provides clinical epidemiology data for unraveling the relationship between OSAS and lung cancer, and our analysis have uncovered insights into the molecular mechanisms underlying pathogenesis of OSASrelated comorbidity
Summary
Epidemiological evidence has suggested that obstructive sleep apnea Syndrome (OSAS) is associated with a higher prevalence of cancer and cancer-related mortality; laboratory-based observations have revealed that constitutive components of OSAS are mechanistically involved in accelerated tumor growth and progression. Little information is available on the association between OSAS and lung cancer. To clarify this possibility, we utilized a hospital-based database to examine whether the presence of OSAS increased lung cancer incidence and risk of progression or mortality from cancer. We performed gene microarray analyses of datasets from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) to evaluate underlying molecular mechanisms that involved in clinic pathological and prognostic features of patients with lung cancer. OSAS is a highly prevalent chronic disease, characterized by repetitive episodes of upper-airway obstruction during sleep. Extensive studies demonstrate that OSAS contributes to developing many diseases such as cardiovascular and metabolic diseases, behavioral and cognitive dysfunction, as well as affects the quality of life [2,3,4,5,6]
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