Integrative Analysis of Hypoxia-Associated Signature in Pan-Cancer.

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.