HIF1A expression correlates with increased tumor immune and stromal signatures and aggressive phenotypes in human cancer
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ORIGINAL PAPER
HIF1A expression correlates with increased tumor immune and stromal signatures and aggressive phenotypes in human cancers Baotao Chen 1,2,3 & Lin Li 1,2,3 & Mengyuan Li 1,2,3 & Xiaosheng Wang 1,2,3 Received: 21 January 2020 / Revised: 12 May 2020 / Accepted: 15 May 2020 # International Society for Cellular Oncology 2020
Abstract Background Although many studies have revealed essential roles of HIF1A (hypoxia inducible factor 1 subunit alpha) in regulating various pathways associated with cancer development, a systematic investigation of associations of HIF1A expression with tumor immunity, the tumor microenvironment and other tumor phenotypes in pan-cancer is lacking. Methods Using cancer genomics datasets of 10 cancer cohorts from the Cancer Genome Atlas (TCGA) program, we investigated associations of HIF1A expression with tumor immune and stromal signatures, and various tumor phenotypes, including cell proliferation, stemness, epithelial-mesenchymal transition (EMT), tumor purity, oncogenic signaling, and clinical outcomes. Results HIF1A upregulation was found to be associated with increased immune and stromal signatures, aggressive phenotypes, and worse survival rates in various cancers. Moreover, HIF1A upregulation was not only associated with activation of various oncogenic signaling pathways, but also with increased tumor suppressive signatures, including apoptosis and anti-tumor immune response, indicative of a dual role of HIF1A in cancer development. However, HIF1A expression showed a stronger correlation with immune-inhibiting signatures than with immune-promoting signatures. Furthermore, HIF1A expression was found to be positively associated with both tumor immune infiltration and PD-L1 expression, indicating that tumors with elevated expression of HIF1A may exhibit a more active immunotherapy response. This indication was substantiated in a kidney cancer cohort receiving anti-PD-1/PD-L1 immunotherapy. Conclusions HIF1A upregulation correlates with increased tumor immune and stromal signatures and aggressive phenotypes in human cancers. Our analysis may provide new insights into the role of HIF1A in tumor biology and clinical management. Keywords HIF1A expression . tumor immunity . tumor stroma . PD-L1 expression . tumor phenotypes
1 Introduction Baotao Chen and Lin Li contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13402-020-00534-4) contains supplementary material, which is available to authorized users. * Xiaosheng Wang [email protected] 1
Biomedical Informatics Research Lab, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China
2
Cancer Genomics Research Center, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 211198, China
3
Big Data Research Institute, China Pharmaceutical University, Nanjing 211198, China
HIF1A (hypoxia inducible factor 1 subunit alpha) plays a prominent role in regulating cellular
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