Integrative Analysis of Hypoxia-Associated Signature in Pan-Cancer

Qian Zhang; Rui Huang; Hanqing Hu; Lei Yu; Qingchao Tang; Yangbao Tao; Zheng Liu; Jiaying Li; Guiyu Wang

doi:10.1016/j.isci.2020.101460

Integrative Analysis of Hypoxia-Associated Signature in Pan-Cancer

iScience. 2020 Aug 14;23(9):101460. doi: 10.1016/j.isci.2020.101460. eCollection 2020 Sep 25.

Authors

Qian Zhang¹, Rui Huang¹, Hanqing Hu¹, Lei Yu¹, Qingchao Tang¹, Yangbao Tao¹, Zheng Liu², Jiaying Li¹, Guiyu Wang¹

Affiliations

¹ Department of Colorectal Surgery, the Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province 150086, China.
² Department of Colorectal Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100000, China.

Abstract

Hypoxia is serving crucial roles in cancers. This study aims to comprehensively analyze the molecular features and clinical relevance of a well-defined hypoxia-associated signature in pan-cancer using multi-omics data. Data were acquired from TCGA, CCLE, GDSC, and GEO. RNA expression pattern, copy number variation (CNV), methylation, and mutation of the signature were analyzed. The majority of the 15 genes were upregulated in cancer tissues compared with normal tissue, and RNA expression was negatively associated with methylation level. CNV occurred in almost all the cancers, whereas mutation frequency was low across different cancer types. The signature was also closely related to cancer hallmarks and cancer-related metabolism pathways. NDRG1 was upregulated in kidney cancer tissues as indicated by immunohistochemistry. Besides, most of the 15 genes were risk factors for patients' overall survival. Our results provide a valuable resource that will guide both mechanistic and therapeutic analyses of the hypoxia signature in cancers.

Keywords: Biological Sciences; Cancer Systems Biology; Genomics.