Whole transcriptome analysis of unmutated sporadic ALS patients' peripheral blood reveals phenotype-specific gene expression signature
Amyotrophic lateral sclerosis (ALS) is an adult neurodegenerative disorder. According to clinical criteria, ALS patients can be classified into eight subgroups: classic, bulbar, pyramidal, pure lower motor neuron, flail arm, pure upper motor neuron, flail leg, and respiratory. There are no well-esta...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-03-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996125000397 |
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| author | Francesca Dragoni Maria Garofalo Rosalinda Di Gerlando Bartolo Rizzo Matteo Bordoni Eveljn Scarian Camilla Viola Veronica Bettoni Giuseppe Fiamingo Danilo Tornabene Lucia Scanu Orietta Pansarasa Luca Diamanti Stella Gagliardi |
| author_facet | Francesca Dragoni Maria Garofalo Rosalinda Di Gerlando Bartolo Rizzo Matteo Bordoni Eveljn Scarian Camilla Viola Veronica Bettoni Giuseppe Fiamingo Danilo Tornabene Lucia Scanu Orietta Pansarasa Luca Diamanti Stella Gagliardi |
| author_sort | Francesca Dragoni |
| collection | DOAJ |
| description | Amyotrophic lateral sclerosis (ALS) is an adult neurodegenerative disorder. According to clinical criteria, ALS patients can be classified into eight subgroups: classic, bulbar, pyramidal, pure lower motor neuron, flail arm, pure upper motor neuron, flail leg, and respiratory. There are no well-established molecular biomarkers for early diagnosis, prognosis, and progression monitoring of this fatal disease. Classification based on clinical phenotypes could be associated with peculiar gene expression patterns shaped during lifespan, allowing the identification of specific sporadic ALS (sALS) subtypes with less heterogeneous clinical and biological features. Our objective was to define a phenotype-specific transcriptomic signature of distinct ALS phenotypes, and lay the foundation for biomarkers development. We characterized 48 sALS patients by clinical and paraclinical parameters, and subdivided them in “Classic” (n = 12), “Bulbar” (n = 10), “Flail Arm” (n = 7), “Flail Leg” (n = 10) and “Pyramidal” (n = 9) phenotypes. RNAs extracted from patients' PBMCs and 19 controls were sequenced. Our analysis allowed the visualization of gene expression differential clusters between patients and controls. Interestingly, only one gene (Y3_RNA, a misc_RNA component of the Ro60 ribonucleoprotein involved in cellular response to interferon-alpha) was upregulated at different levels across all phenotypes, whereas other genes appeared phenotype-specific. The work proposed stress the innovative view of ALS as a multi-systemic disorder rather than a pure motor neuron-associated and ‘neurocentric’ pathology. The possibility to cluster ALS patients based on their molecular signature pave the way for future personalized clinical trials and early diagnosis. |
| format | Article |
| id | doaj-art-732ef72f84914470aa45b69b82fe1ca0 |
| institution | Kabale University |
| issn | 1095-953X |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj-art-732ef72f84914470aa45b69b82fe1ca02025-02-08T04:59:33ZengElsevierNeurobiology of Disease1095-953X2025-03-01206106823Whole transcriptome analysis of unmutated sporadic ALS patients' peripheral blood reveals phenotype-specific gene expression signatureFrancesca Dragoni0Maria Garofalo1Rosalinda Di Gerlando2Bartolo Rizzo3Matteo Bordoni4Eveljn Scarian5Camilla Viola6Veronica Bettoni7Giuseppe Fiamingo8Danilo Tornabene9Lucia Scanu10Orietta Pansarasa11Luca Diamanti12Stella Gagliardi13IRCCS Mondino Foundation, Pavia, ItalyIRCCS Mondino Foundation, Pavia, ItalyIRCCS Mondino Foundation, Pavia, Italy; University of Pavia, Pavia, ItalyIRCCS Mondino Foundation, Pavia, ItalyIRCCS Mondino Foundation, Pavia, ItalyIRCCS Mondino Foundation, Pavia, ItalyIRCCS Mondino Foundation, Pavia, Italy; University of Pavia, Pavia, ItalyIRCCS Mondino Foundation, Pavia, Italy; University of Pavia, Pavia, ItalyIRCCS Mondino Foundation, Pavia, Italy; University of Pavia, Pavia, ItalyIRCCS Mondino Foundation, Pavia, Italy; University of Pavia, Pavia, ItalyIRCCS Mondino Foundation, Pavia, Italy; University of Pavia, Pavia, ItalyIRCCS Mondino Foundation, Pavia, ItalyIRCCS Mondino Foundation, Pavia, ItalyIRCCS Mondino Foundation, Pavia, Italy; Corresponding author.Amyotrophic lateral sclerosis (ALS) is an adult neurodegenerative disorder. According to clinical criteria, ALS patients can be classified into eight subgroups: classic, bulbar, pyramidal, pure lower motor neuron, flail arm, pure upper motor neuron, flail leg, and respiratory. There are no well-established molecular biomarkers for early diagnosis, prognosis, and progression monitoring of this fatal disease. Classification based on clinical phenotypes could be associated with peculiar gene expression patterns shaped during lifespan, allowing the identification of specific sporadic ALS (sALS) subtypes with less heterogeneous clinical and biological features. Our objective was to define a phenotype-specific transcriptomic signature of distinct ALS phenotypes, and lay the foundation for biomarkers development. We characterized 48 sALS patients by clinical and paraclinical parameters, and subdivided them in “Classic” (n = 12), “Bulbar” (n = 10), “Flail Arm” (n = 7), “Flail Leg” (n = 10) and “Pyramidal” (n = 9) phenotypes. RNAs extracted from patients' PBMCs and 19 controls were sequenced. Our analysis allowed the visualization of gene expression differential clusters between patients and controls. Interestingly, only one gene (Y3_RNA, a misc_RNA component of the Ro60 ribonucleoprotein involved in cellular response to interferon-alpha) was upregulated at different levels across all phenotypes, whereas other genes appeared phenotype-specific. The work proposed stress the innovative view of ALS as a multi-systemic disorder rather than a pure motor neuron-associated and ‘neurocentric’ pathology. The possibility to cluster ALS patients based on their molecular signature pave the way for future personalized clinical trials and early diagnosis.http://www.sciencedirect.com/science/article/pii/S0969996125000397sALSAmyotrophic lateral sclerosisPhenotypesRNA-seqBulbarClassic |
| spellingShingle | Francesca Dragoni Maria Garofalo Rosalinda Di Gerlando Bartolo Rizzo Matteo Bordoni Eveljn Scarian Camilla Viola Veronica Bettoni Giuseppe Fiamingo Danilo Tornabene Lucia Scanu Orietta Pansarasa Luca Diamanti Stella Gagliardi Whole transcriptome analysis of unmutated sporadic ALS patients' peripheral blood reveals phenotype-specific gene expression signature Neurobiology of Disease sALS Amyotrophic lateral sclerosis Phenotypes RNA-seq Bulbar Classic |
| title | Whole transcriptome analysis of unmutated sporadic ALS patients' peripheral blood reveals phenotype-specific gene expression signature |
| title_full | Whole transcriptome analysis of unmutated sporadic ALS patients' peripheral blood reveals phenotype-specific gene expression signature |
| title_fullStr | Whole transcriptome analysis of unmutated sporadic ALS patients' peripheral blood reveals phenotype-specific gene expression signature |
| title_full_unstemmed | Whole transcriptome analysis of unmutated sporadic ALS patients' peripheral blood reveals phenotype-specific gene expression signature |
| title_short | Whole transcriptome analysis of unmutated sporadic ALS patients' peripheral blood reveals phenotype-specific gene expression signature |
| title_sort | whole transcriptome analysis of unmutated sporadic als patients peripheral blood reveals phenotype specific gene expression signature |
| topic | sALS Amyotrophic lateral sclerosis Phenotypes RNA-seq Bulbar Classic |
| url | http://www.sciencedirect.com/science/article/pii/S0969996125000397 |
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