Deciphering human endogenous retrovirus expression in colorectal cancers: exploratory analysis regarding prognostic value in liver metastasesResearch in context
Summary: Background: Human Endogenous RetroVirus (HERV) expression in tumours reflects epigenetic dysregulation of cancer and an oncogenic factor through promoter/enhancer action on genes. While more than 50% of colorectal cancers develop liver metastases, HERV has not been studied in this context....
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Elsevier
2025-06-01
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396425001719 |
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| author | Julien Viot Romain Loyon Nawfel Adib Pierre Laurent-Puig Aurélien de Reyniès Fabrice André Franck Monnien Thierry André Magali Svrcek Anthony Turpin Zohair Selmani Laurent Arnould Laura Guyard Nicolas Gilbert Anthony Boureux Olivier Adotevi Angélique Vienot Syrine Abdeljaoued Dewi Vernerey Christophe Borg Daniel Gautheret |
| author_facet | Julien Viot Romain Loyon Nawfel Adib Pierre Laurent-Puig Aurélien de Reyniès Fabrice André Franck Monnien Thierry André Magali Svrcek Anthony Turpin Zohair Selmani Laurent Arnould Laura Guyard Nicolas Gilbert Anthony Boureux Olivier Adotevi Angélique Vienot Syrine Abdeljaoued Dewi Vernerey Christophe Borg Daniel Gautheret |
| author_sort | Julien Viot |
| collection | DOAJ |
| description | Summary: Background: Human Endogenous RetroVirus (HERV) expression in tumours reflects epigenetic dysregulation of cancer and an oncogenic factor through promoter/enhancer action on genes. While more than 50% of colorectal cancers develop liver metastases, HERV has not been studied in this context. Methods: We collected 400 RNA-seq samples from over 200 patients with primary and liver metastases, including public data and a novel set of 200 samples. Findings: We observed global stability of HERV expression between liver metastases and primary colorectal cancers, suggesting an early oncogenic footprint. We identified a list of 17 HERV loci for liver metastatic colorectal cancer (lmCRC) characterization; with tumour-specificity validated in single-cell metastatic colorectal cancer data and normal tissue bulk RNA-seq. Eleven loci produced HERV-derived peptides as per tandem mass spectrometry from primary colorectal cancer. Six loci were associated with the risk of relapse after lmCRC surgery. Four, HERVH_Xp22.32a, HERVH_20p11.23b, HERVH_13q33.3, HERVH_13q31.3, had adverse prognostic value (log-rank p-value 0.028, 0.0083, 9e-4, 0.05, respectively) while two, HERVH_Xp22.2c (log-rank p-value 0.032) and HERVH_8q21.3b (in multivariable models) were associated with better prognosis. Moreover, the markers showed a cumulative effect on survival when expressed. Some were associated with decreased cytotoxic immune cells and most of them correlated with cell cycle pathways. Interpretation: These findings provide insights into the lmCRC transcriptome landscape by suggesting prognostic markers and potential therapeutic targets. Funding: This work was supported by funding from institutional grants from Inserm, EFS, University of Bourgogne Franche-Comté, national found “Agence Nationale de la Recherche – ANR-JCJC: Projet HERIC and ANR-22-CE45-0007”, and “La ligue contre le cancer”. |
| format | Article |
| id | doaj-art-5b6f15dbd6c54df6bdb9b3b13cc5682a |
| institution | Kabale University |
| issn | 2352-3964 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
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| spelling | doaj-art-5b6f15dbd6c54df6bdb9b3b13cc5682a2025-08-20T03:49:41ZengElsevierEBioMedicine2352-39642025-06-0111610572710.1016/j.ebiom.2025.105727Deciphering human endogenous retrovirus expression in colorectal cancers: exploratory analysis regarding prognostic value in liver metastasesResearch in contextJulien Viot0Romain Loyon1Nawfel Adib2Pierre Laurent-Puig3Aurélien de Reyniès4Fabrice André5Franck Monnien6Thierry André7Magali Svrcek8Anthony Turpin9Zohair Selmani10Laurent Arnould11Laura Guyard12Nicolas Gilbert13Anthony Boureux14Olivier Adotevi15Angélique Vienot16Syrine Abdeljaoued17Dewi Vernerey18Christophe Borg19Daniel Gautheret20Département d’Oncologie Médicale, CHU Besançon, Besançon 25000, France; Université Marie et Louis Pasteur, INSERM, Etablissement Français du Sang Bourgogne Franche-Comté, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, Besançon, France; Corresponding author. CHU Besançon, Département d’Oncologie Médicale, Besançon 25000, France.Université Marie et Louis Pasteur, INSERM, Etablissement Français du Sang Bourgogne Franche-Comté, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, Besançon, FranceUniversité Marie et Louis Pasteur, INSERM, Etablissement Français du Sang Bourgogne Franche-Comté, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, Besançon, FranceDepartment of Biology, Institut du Cancer Paris CARPEM, APHP, APHP.Centre-Université Paris Cité, Hôpital Européen G. Pompidou, Paris, France; Centre de Recherche des Cordeliers, Sorbonne Université, INSERM, Université de Paris, EPIGENETEC, Paris 75006, FranceCentre de Recherche des Cordeliers, Sorbonne Université, INSERM, Université de Paris, EPIGENETEC, Paris 75006, FranceParis-Saclay University, Gustave Roussy, Villejuif, France; Department of Medical Oncology, Gustave Roussy, Villejuif, FranceDépartement d’Oncologie Médicale, CHU Besançon, Besançon 25000, France; Université Marie et Louis Pasteur, INSERM, Etablissement Français du Sang Bourgogne Franche-Comté, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, Besançon, FranceDepartment of Medical Oncology, Sorbonne University, Saint-Antoine Hospital, AP-HP, Paris, FranceDepartment of Pathology, Saint-Antoine Hospital, AP-HP, Sorbonne Université, Paris, FranceDepartment of Oncology, Lille University Hospital, France; CNRS UMR9020, INSERM UMR1277, University of Lille, Institut Pasteur, Lille, FranceDépartement d’Oncologie Médicale, CHU Besançon, Besançon 25000, France; Université Marie et Louis Pasteur, INSERM, Etablissement Français du Sang Bourgogne Franche-Comté, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, Besançon, FranceDepartment of Tumour Biology and Pathology, Georges François Leclerc Cancer Center - UNICANCER, Dijon, France; CCRB Ferdinand Cabanne de Dijon, FranceDepartment of Tumour Biology and Pathology, Georges François Leclerc Cancer Center - UNICANCER, Dijon, France; CCRB Ferdinand Cabanne de Dijon, FranceIRMB, INSERM U1183, Hopital Saint-Eloi, Universite de Montpellier, Montpellier, FranceIRMB, INSERM U1183, Hopital Saint-Eloi, Universite de Montpellier, Montpellier, FranceDépartement d’Oncologie Médicale, CHU Besançon, Besançon 25000, France; Université Marie et Louis Pasteur, INSERM, Etablissement Français du Sang Bourgogne Franche-Comté, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, Besançon, FranceDépartement d’Oncologie Médicale, CHU Besançon, Besançon 25000, France; Université Marie et Louis Pasteur, INSERM, Etablissement Français du Sang Bourgogne Franche-Comté, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, Besançon, FranceUniversité Marie et Louis Pasteur, INSERM, Etablissement Français du Sang Bourgogne Franche-Comté, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, Besançon, FranceDépartement d’Oncologie Médicale, CHU Besançon, Besançon 25000, FranceDépartement d’Oncologie Médicale, CHU Besançon, Besançon 25000, France; Université Marie et Louis Pasteur, INSERM, Etablissement Français du Sang Bourgogne Franche-Comté, UMR1098, Interactions Hôte-Greffon-Tumeur/Ingénierie Cellulaire et Génique, Besançon, FranceInstitute for Integrative Biology of the Cell (I2BC), Université Paris-Saclay, CNRS, CEA, Gif-sur-Yvette 91190, FranceSummary: Background: Human Endogenous RetroVirus (HERV) expression in tumours reflects epigenetic dysregulation of cancer and an oncogenic factor through promoter/enhancer action on genes. While more than 50% of colorectal cancers develop liver metastases, HERV has not been studied in this context. Methods: We collected 400 RNA-seq samples from over 200 patients with primary and liver metastases, including public data and a novel set of 200 samples. Findings: We observed global stability of HERV expression between liver metastases and primary colorectal cancers, suggesting an early oncogenic footprint. We identified a list of 17 HERV loci for liver metastatic colorectal cancer (lmCRC) characterization; with tumour-specificity validated in single-cell metastatic colorectal cancer data and normal tissue bulk RNA-seq. Eleven loci produced HERV-derived peptides as per tandem mass spectrometry from primary colorectal cancer. Six loci were associated with the risk of relapse after lmCRC surgery. Four, HERVH_Xp22.32a, HERVH_20p11.23b, HERVH_13q33.3, HERVH_13q31.3, had adverse prognostic value (log-rank p-value 0.028, 0.0083, 9e-4, 0.05, respectively) while two, HERVH_Xp22.2c (log-rank p-value 0.032) and HERVH_8q21.3b (in multivariable models) were associated with better prognosis. Moreover, the markers showed a cumulative effect on survival when expressed. Some were associated with decreased cytotoxic immune cells and most of them correlated with cell cycle pathways. Interpretation: These findings provide insights into the lmCRC transcriptome landscape by suggesting prognostic markers and potential therapeutic targets. Funding: This work was supported by funding from institutional grants from Inserm, EFS, University of Bourgogne Franche-Comté, national found “Agence Nationale de la Recherche – ANR-JCJC: Projet HERIC and ANR-22-CE45-0007”, and “La ligue contre le cancer”.http://www.sciencedirect.com/science/article/pii/S2352396425001719Transposable elementsEndogenous retrovirusColorectal cancerLiver metastasesImmunology |
| spellingShingle | Julien Viot Romain Loyon Nawfel Adib Pierre Laurent-Puig Aurélien de Reyniès Fabrice André Franck Monnien Thierry André Magali Svrcek Anthony Turpin Zohair Selmani Laurent Arnould Laura Guyard Nicolas Gilbert Anthony Boureux Olivier Adotevi Angélique Vienot Syrine Abdeljaoued Dewi Vernerey Christophe Borg Daniel Gautheret Deciphering human endogenous retrovirus expression in colorectal cancers: exploratory analysis regarding prognostic value in liver metastasesResearch in context EBioMedicine Transposable elements Endogenous retrovirus Colorectal cancer Liver metastases Immunology |
| title | Deciphering human endogenous retrovirus expression in colorectal cancers: exploratory analysis regarding prognostic value in liver metastasesResearch in context |
| title_full | Deciphering human endogenous retrovirus expression in colorectal cancers: exploratory analysis regarding prognostic value in liver metastasesResearch in context |
| title_fullStr | Deciphering human endogenous retrovirus expression in colorectal cancers: exploratory analysis regarding prognostic value in liver metastasesResearch in context |
| title_full_unstemmed | Deciphering human endogenous retrovirus expression in colorectal cancers: exploratory analysis regarding prognostic value in liver metastasesResearch in context |
| title_short | Deciphering human endogenous retrovirus expression in colorectal cancers: exploratory analysis regarding prognostic value in liver metastasesResearch in context |
| title_sort | deciphering human endogenous retrovirus expression in colorectal cancers exploratory analysis regarding prognostic value in liver metastasesresearch in context |
| topic | Transposable elements Endogenous retrovirus Colorectal cancer Liver metastases Immunology |
| url | http://www.sciencedirect.com/science/article/pii/S2352396425001719 |
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