Immune-focused multi-omics analysis of prostate cancer: leukocyte Ig-Like receptors are associated with disease progression
| Autor: | Colin Collins, Paul C. Boutros, Marie-Laure Martin-Magniette, Xavier-Philippe Légaré, Benjamin Vittrant, Alain Bergeron, Arnaud Droit, Hélène Hovington, Yves Fradet, Oscar Eduardo Molina, Julie Livingstone, Mickael Leclercq, Valérie Picard |
|---|---|
| Přispěvatelé: | Computational Biology Laboratory, CHU de Québec–Université Laval, Université Laval [Québec] (ULaval)-Université Laval [Québec] (ULaval), Laboratoire d'Uro-Oncologie Expérimentale, Institut des Sciences des Plantes de Paris-Saclay (IPS2 (UMR_9213 / UMR_1403)), Université d'Évry-Val-d'Essonne (UEVE)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Departments of Human Genetics & Urology, Jonsson Comprehensive Cancer Center and Institute for Precision Health, University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC)-University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), Departments of Medical Biophysics and Pharmacology & Toxicology, University of Toronto, Vancouver Prostate Cancer Centre, Laboratoire d'Uro-Oncologie Experimentale Terry Fox Research Institute New Frontier Program 1062, Université d'Évry-Val-d'Essonne (UEVE)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of California-University of California-University of California [Los Angeles] (UCLA), University of California-University of California |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Aging medicine.medical_treatment Disease Prostate cancer 0302 clinical medicine Leukocytes biochemical recurrence Immunology and Allergy RC254-282 Original Research Cancer breakpoint cluster region Neoplasms. Tumors. Oncology. Including cancer and carcinogens 3. Good health Oncology Local multi-omics analysis leukocyte Ig-Like Receptors 030220 oncology & carcinogenesis Disease Progression [SDV.IMM]Life Sciences [q-bio]/Immunology immunotherapy Antibody Research Article Biotechnology Biochemical recurrence Urologic Diseases Immunology Oncology and Carcinogenesis Immunoglobulins Biology 03 medical and health sciences Immune system microRNA medicine Genetics Humans Prevention Human Genome Prostatic Neoplasms Immunotherapy RC581-607 medicine.disease 030104 developmental biology Neoplasm Recurrence Cancer research biology.protein Immunization Neoplasm Recurrence Local Immunologic diseases. Allergy |
| Zdroj: | OncoImmunology OncoImmunology, 2020, 9 (1), pp.1851950. ⟨10.1080/2162402X.2020.1851950⟩ OncoImmunology, Vol 9, Iss 1 (2020) OncoImmunology, Taylor & Francis, 2020, 9 (1), pp.1851950. ⟨10.1080/2162402X.2020.1851950⟩ Oncoimmunology, vol 9, iss 1 Oncoimmunology article-version (VoR) Version of Record |
| ISSN: | 2162-4011 2162-402X |
| DOI: | 10.1080/2162402X.2020.1851950⟩ |
| Popis: | International audience; Prostate cancer (PCa) immunotherapy has shown limited efficacy so far, even in advanced-stage cancers. The success rate of PCa immunotherapy might be improved by approaches more adapted to the immunobiology of the disease. The objective of this study was to perform a multi-omics analysis to identify immune genes associated with PCa progression to better characterize PCa immunobiology and propose new immunotherapeutic targets. mRNA, miRNA, methylation, copy number aberration, and single nucleotide variant datasets from The Cancer Genome Atlas PRAD cohort were analyzed after filtering for genes associated with immunity. Sparse partial least squares-discriminant analyses were performed to identify features associated with biochemical recurrence (BCR) in each type of omics data. Selected features predicted BCR with a balanced error rate (BER) of 0.20 to 0.51 in single-omics and of 0.05 in multi-omics analyses. Amongst features associated with BCR were genes from the Immunoglobulin Ig-like Receptor (LILR) family which are immune checkpoints with immunotherapeutic potential. Using Multivariate INTegrative (MINT) analysis, the association of five LILR genes with BCR was quantified in a combination of three RNA-seq datasets and confirmed with Kaplan-Meier analysis in both these and in an independent RNA-seq dataset. Finally, immunohistochemistry showed that a high number of LILRB1 positive cells within the tumors predicted long-term adverse outcomes. Thus, tumors characterized by abnormal expression of LILR genes have an elevated risk of recurring after definitive local therapy. The immunotherapeutic potential of these regulators to stimulate the immune response against PCa should be evaluated in pre-clinical models. |
| Databáze: | OpenAIRE |
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