1. Therapeutic potential of the human endogenous retroviral envelope protein HEMO: a pan-cancer analysis
- Author
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Jean-Yves Scoazec, Christophe Massard, Odile Heidmann, Kévin De Azevedo, Olivia Bawa, Bastien Job, Amélie Kasperek, Thierry Heidmann, Anthony Béguin, UMR9196, Physiologie et Pathologie Moléculaires des Rétrovirus Endogènes et Infectieux, Physiologie et physiopathologie des rétrovirus endogènes et infectieux (RETRO-ENDO), Institut Gustave Roussy (IGR)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse (AMMICa), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Département d’Innovation Thérapeutique et essais précoces [Gustave Roussy] (DITEP), Institut Gustave Roussy (IGR), and HEIDMANN, Odile
- Subjects
gene set enrichment analysis ,Cancer Research ,retroviruses ,[SDV]Life Sciences [q-bio] ,Cell ,Rétrovirus endogène ,The Cancer Genome Atlas ,Biology ,Genome ,Transcriptome ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Wnt/b-catenin ERVMER34-1 ,Gene expression ,Genetics ,medicine ,cancer ,Humans ,HEMO ,Gene ,Wnt Signaling Pathway ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology ,0303 health sciences ,GSEA ,human endogenous MER34 ORF ,Endogenous Retroviruses ,Wnt signaling pathway ,Cancer ,General Medicine ,TCGA ,medicine.disease ,ERVMER34-1 ,3. Good health ,Biomarker (cell) ,Endometrial Neoplasms ,[SDV] Life Sciences [q-bio] ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,endogenous retrovirus medium-reiteration-family-34 member 1 ,Cancer research ,Molecular Medicine ,HERV ,Female - Abstract
Human endogenous retroviruses (HERVs) represent approximately 8% of our genome. Most of these sequences are defective except for a few genes such as the ancestral retroviral HEMO envelope gene (Human Endogenous MER34 ORF), recently characterized by our group. In this study, we characterized transcriptional activation of HEMO in primary tumors from The Cancer Genome Atlas (TCGA) and in metastatic tumors from a Gustave Roussy cohort. Pan-cancer detection of the HEMO protein in a series of patient samples validated these results. Differential gene expression analysis in various TCGA datasets revealed a link between HEMO expression and activation of Wnt/β-catenin signaling, in particular in endometrial cancer. Studies on cell models led us to propose that the Wnt/β-catenin pathway could act as an upstream regulator of this retroviral endogenous sequence in tumor condition. Characterization of transcriptomic profiles of both HEMOLow and HEMOHigh tumors suggested that activation of HEMO is negatively associated with immune response signatures. Taken together, these results highlight that HEMO, as an endogenous retroviral envelope protein specifically expressed in tumors, represents a promising tumor biomarker and therapeutic target.
- Published
- 2021
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