Li Lifeng, Lu Jingli, Xue Wenhua, Wang Liping, Zhai Yunkai, Fan Zhirui, Wu Ge, Fan Feifei, Li Jieyao, Zhang Chaoqi, Zhang Yi, Zhao Jie
Biotherapy Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
Oncotarget. 2017 Mar 28;8(13):21567-21578. doi: 10.18632/oncotarget.15372.
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.
基于我们医院的数据库,阻塞性睡眠呼吸暂停综合征(OSAS)患者中肺癌诊断的发生率与医院普通人群相似;在被诊断为肺癌的个体中,OSAS的存在与死亡风险增加相关。在基因表达和网络水平信息方面,我们揭示了缺氧条件下肺癌细胞中与HIF1和代谢途径相关分子的显著改变。我们还观察到GBE1和HK2是缺氧条件下肺癌细胞中HIF1途径的下游分子。此外,我们使用公开可用的数据集验证了晚期肺腺癌患者的HK2和GBE1表达高于早期患者。在预后特征方面,生存分析显示,GBE1和HK2高表达组的肺腺癌患者生存率较差。通过分析和整合多个数据集,我们确定了缺氧与肺癌之间的分子趋同,这反映了它们的临床特征,并揭示了缺氧诱导肺癌进展所涉及的分子途径。总之,我们表明OSAS严重程度似乎会增加肺癌死亡风险。