Blood transcriptomics of drug-naïve sporadic Parkinson's disease patients

Raffaella Calligaris, Mihaela Banica, Paola Roncaglia, Elisa Robotti, Sara Finaurini, Christina Vlachouli, Lucia Antonutti, Francesco Iorio, Annamaria Carissimo, Tatiana Cattaruzza, Andrea Ceiner, Dejan Lazarevic, Alberto Cucca, Nicola Pangher, Emilio Marengo, Diego di Bernardo, Gilberto Pizzolato, Stefano Gustincich

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Background: Parkinson's disease (PD) is a chronic progressive neurodegenerative disorder that is clinically defined in terms of motor symptoms. These are preceded by prodromal non-motor manifestations that prove the systemic nature of the disease. Identifying genes and pathways altered in living patients provide new information on the diagnosis and pathogenesis of sporadic PD. Methods: Changes in gene expression in the blood of 40 sporadic PD patients and 20 healthy controls ("Discovery set") were analyzed by taking advantage of the Affymetrix platform. Patients were at the onset of motor symptoms and before initiating any pharmacological treatment. Data analysis was performed by applying Ranking-Principal Component Analysis, PUMA and Significance Analysis of Microarrays. Functional annotations were assigned using GO, DAVID, GSEA to unveil significant enriched biological processes in the differentially expressed genes. The expressions of selected genes were validated using RT-qPCR and samples from an independent cohort of 12 patients and controls ("Validation set"). Results: Gene expression profiling of blood samples discriminates PD patients from healthy controls and identifies differentially expressed genes in blood. The majority of these are also present in dopaminergic neurons of the Substantia Nigra, the key site of neurodegeneration. Together with neuronal apoptosis, lymphocyte activation and mitochondrial dysfunction, already found in previous analysis of PD blood and post-mortem brains, we unveiled transcriptome changes enriched in biological terms related to epigenetic modifications including chromatin remodeling and methylation. Candidate transcripts as CBX5, TCF3, MAN1C1 and DOCK10 were validated by RT-qPCR. Conclusions: Our data support the use of blood transcriptomics to study neurodegenerative diseases. It identifies changes in crucial components of chromatin remodeling and methylation machineries as early events in sporadic PD suggesting epigenetics as target for therapeutic intervention.

Original languageEnglish
Article number876
JournalBMC Genomics
Volume16
Issue number1
DOIs
Publication statusPublished - Oct 28 2015

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Parkinson Disease
Pharmaceutical Preparations
Chromatin Assembly and Disassembly
Epigenomics
Neurodegenerative Diseases
Methylation
Genes
Biological Phenomena
Gene Expression
Dopaminergic Neurons
Gene Expression Profiling
Substantia Nigra
Microarray Analysis
Lymphocyte Activation
Principal Component Analysis
Transcriptome
Pharmacology
Apoptosis
Brain
Therapeutics

Keywords

  • Blood transcriptomics
  • de novo
  • Drug-naïve patients
  • Parkinson's disease

ASJC Scopus subject areas

  • Biotechnology
  • Genetics

Cite this

Calligaris, R., Banica, M., Roncaglia, P., Robotti, E., Finaurini, S., Vlachouli, C., ... Gustincich, S. (2015). Blood transcriptomics of drug-naïve sporadic Parkinson's disease patients. BMC Genomics, 16(1), [876]. https://doi.org/10.1186/s12864-015-2058-3

Blood transcriptomics of drug-naïve sporadic Parkinson's disease patients. / Calligaris, Raffaella; Banica, Mihaela; Roncaglia, Paola; Robotti, Elisa; Finaurini, Sara; Vlachouli, Christina; Antonutti, Lucia; Iorio, Francesco; Carissimo, Annamaria; Cattaruzza, Tatiana; Ceiner, Andrea; Lazarevic, Dejan; Cucca, Alberto; Pangher, Nicola; Marengo, Emilio; di Bernardo, Diego; Pizzolato, Gilberto; Gustincich, Stefano.

In: BMC Genomics, Vol. 16, No. 1, 876, 28.10.2015.

Research output: Contribution to journalArticle

Calligaris, R, Banica, M, Roncaglia, P, Robotti, E, Finaurini, S, Vlachouli, C, Antonutti, L, Iorio, F, Carissimo, A, Cattaruzza, T, Ceiner, A, Lazarevic, D, Cucca, A, Pangher, N, Marengo, E, di Bernardo, D, Pizzolato, G & Gustincich, S 2015, 'Blood transcriptomics of drug-naïve sporadic Parkinson's disease patients', BMC Genomics, vol. 16, no. 1, 876. https://doi.org/10.1186/s12864-015-2058-3
Calligaris R, Banica M, Roncaglia P, Robotti E, Finaurini S, Vlachouli C et al. Blood transcriptomics of drug-naïve sporadic Parkinson's disease patients. BMC Genomics. 2015 Oct 28;16(1). 876. https://doi.org/10.1186/s12864-015-2058-3
Calligaris, Raffaella ; Banica, Mihaela ; Roncaglia, Paola ; Robotti, Elisa ; Finaurini, Sara ; Vlachouli, Christina ; Antonutti, Lucia ; Iorio, Francesco ; Carissimo, Annamaria ; Cattaruzza, Tatiana ; Ceiner, Andrea ; Lazarevic, Dejan ; Cucca, Alberto ; Pangher, Nicola ; Marengo, Emilio ; di Bernardo, Diego ; Pizzolato, Gilberto ; Gustincich, Stefano. / Blood transcriptomics of drug-naïve sporadic Parkinson's disease patients. In: BMC Genomics. 2015 ; Vol. 16, No. 1.
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AU - Calligaris, Raffaella

AU - Banica, Mihaela

AU - Roncaglia, Paola

AU - Robotti, Elisa

AU - Finaurini, Sara

AU - Vlachouli, Christina

AU - Antonutti, Lucia

AU - Iorio, Francesco

AU - Carissimo, Annamaria

AU - Cattaruzza, Tatiana

AU - Ceiner, Andrea

AU - Lazarevic, Dejan

AU - Cucca, Alberto

AU - Pangher, Nicola

AU - Marengo, Emilio

AU - di Bernardo, Diego

AU - Pizzolato, Gilberto

AU - Gustincich, Stefano

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N2 - Background: Parkinson's disease (PD) is a chronic progressive neurodegenerative disorder that is clinically defined in terms of motor symptoms. These are preceded by prodromal non-motor manifestations that prove the systemic nature of the disease. Identifying genes and pathways altered in living patients provide new information on the diagnosis and pathogenesis of sporadic PD. Methods: Changes in gene expression in the blood of 40 sporadic PD patients and 20 healthy controls ("Discovery set") were analyzed by taking advantage of the Affymetrix platform. Patients were at the onset of motor symptoms and before initiating any pharmacological treatment. Data analysis was performed by applying Ranking-Principal Component Analysis, PUMA and Significance Analysis of Microarrays. Functional annotations were assigned using GO, DAVID, GSEA to unveil significant enriched biological processes in the differentially expressed genes. The expressions of selected genes were validated using RT-qPCR and samples from an independent cohort of 12 patients and controls ("Validation set"). Results: Gene expression profiling of blood samples discriminates PD patients from healthy controls and identifies differentially expressed genes in blood. The majority of these are also present in dopaminergic neurons of the Substantia Nigra, the key site of neurodegeneration. Together with neuronal apoptosis, lymphocyte activation and mitochondrial dysfunction, already found in previous analysis of PD blood and post-mortem brains, we unveiled transcriptome changes enriched in biological terms related to epigenetic modifications including chromatin remodeling and methylation. Candidate transcripts as CBX5, TCF3, MAN1C1 and DOCK10 were validated by RT-qPCR. Conclusions: Our data support the use of blood transcriptomics to study neurodegenerative diseases. It identifies changes in crucial components of chromatin remodeling and methylation machineries as early events in sporadic PD suggesting epigenetics as target for therapeutic intervention.

AB - Background: Parkinson's disease (PD) is a chronic progressive neurodegenerative disorder that is clinically defined in terms of motor symptoms. These are preceded by prodromal non-motor manifestations that prove the systemic nature of the disease. Identifying genes and pathways altered in living patients provide new information on the diagnosis and pathogenesis of sporadic PD. Methods: Changes in gene expression in the blood of 40 sporadic PD patients and 20 healthy controls ("Discovery set") were analyzed by taking advantage of the Affymetrix platform. Patients were at the onset of motor symptoms and before initiating any pharmacological treatment. Data analysis was performed by applying Ranking-Principal Component Analysis, PUMA and Significance Analysis of Microarrays. Functional annotations were assigned using GO, DAVID, GSEA to unveil significant enriched biological processes in the differentially expressed genes. The expressions of selected genes were validated using RT-qPCR and samples from an independent cohort of 12 patients and controls ("Validation set"). Results: Gene expression profiling of blood samples discriminates PD patients from healthy controls and identifies differentially expressed genes in blood. The majority of these are also present in dopaminergic neurons of the Substantia Nigra, the key site of neurodegeneration. Together with neuronal apoptosis, lymphocyte activation and mitochondrial dysfunction, already found in previous analysis of PD blood and post-mortem brains, we unveiled transcriptome changes enriched in biological terms related to epigenetic modifications including chromatin remodeling and methylation. Candidate transcripts as CBX5, TCF3, MAN1C1 and DOCK10 were validated by RT-qPCR. Conclusions: Our data support the use of blood transcriptomics to study neurodegenerative diseases. It identifies changes in crucial components of chromatin remodeling and methylation machineries as early events in sporadic PD suggesting epigenetics as target for therapeutic intervention.

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