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pmid:40748556

Meta-Analysis of Gene Expression Reveals the Core Transcriptomic Profile of Lesional Scalp in Alopecia Areata.

Irene Rivera-Ruiz · Jesús Gay-Mimbrera · Pedro J Gómez-Arias · Macarena Aguilar-Luque · Miguel Juan-Cencerrado · Carmen Mochón-Jiménez · Esmeralda Parra-Peralbo · Beatriz Isla-Tejera · Francisco Gómez-García · Juan Ruano

Dermatology and therapy · 2025 doi:10.1007/s13555-025-01471-6

Paper

complete

Experiment

complete

Data

partial

Analysis

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Execution

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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title
Meta-Analysis of Gene Expression Reveals the Core Transcriptomic Profile of Lesional Scalp in Alopecia Areata.
doi
10.1007/s13555-025-01471-6
pmid
40748556
authors array · 10 items
[0]
Irene Rivera-Ruiz
[1]
Jesús Gay-Mimbrera
[2]
Pedro J Gómez-Arias
[3]
Macarena Aguilar-Luque
[4]
Miguel Juan-Cencerrado
[5]
Carmen Mochón-Jiménez
[6]
Esmeralda Parra-Peralbo
[7]
Beatriz Isla-Tejera
[8]
Francisco Gómez-García
[9]
Juan Ruano
journal
Dermatology and therapy
year
2025
abstract
INTRODUCTION: Alopecia areata (AA) is an immune-mediated inflammatory skin disease that targets hair follicles. Current research yields varied lists of differentially expressed genes (DEGs). A meta-analytic approach is essential to consolidate these findings into a consistent tissue signature. This study aimed to perform a meta-analysis of gene expression datasets to establish a comprehensive molecular signature of AA lesional scalp. METHODS: We conducted a meta-analysis of transcriptomic data from human studies on lesional skin gene expression in AA. Reanalyzing 132 samples (82 patients with AA and 50 controls) from five Gene Expression Omnibus (GEO) datasets (GSE68801, GSE45512, GSE80342, GSE58573, GSE74761), we employed an effect size approach within a random-effects model to identify unique and shared DEGs and enriched biological pathways. The protocol is registered in PROSPERO (CRD42024559847). RESULTS: The meta-analysis identified 5109 DEGs, with 2710 upregulated and 2399 downregulated genes, significantly more than the 120 DEGs shared across the five studies. Consistently expressed genes included CXCL9, CCL18, CXCL10, CD8A, and GZMB (FDR < 0.05). The analysis highlighted chemokines/receptors (CCL13, CCR1, XCL1) and markers of cytotoxic T lymphocytes (GZMA, GZMH, GZMK) and NK cells (NKG2A, NKG2D). Downregulated genes involved type I (KRT31-35, KRT38) and type II (KRT81-86) keratins and proteins crucial for hair follicle structure and function (PADI3, GPRC5D, DSG4, FGF18). Functional analysis showed enrichment in Th1, Th2, and Th17 pathways, particularly through JAK-STAT signaling (p < 0.01). CONCLUSION: This core transcriptome of AA lesions provides new insights into the disease's pathogenesis and identifies potential targets for treatment.
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After categorizing genes from the GEO datasets into AA or control groups, a random-effects model incorporating an effect-size approach was used to manage batch effects and harmonize data across studies. Z-scores derived from p values were crucial for evaluating the consistency and scale of gene expression variations. The false discovery rate (FDR) was controlled via the Benjamini/Hochberg method, setting a significance threshold at FDR < 0.05.
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sections[6] "Meta-Analysis" paragraph 2
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After categorizing genes from the GEO datasets into AA or control groups, a random-effects model incorporating an effect-size approach was used to manage batch effects and harmonize data across studies. Z-scores derived from p values were crucial for evaluating the consistency and scale of gene expression variations. The false discovery rate (FDR) was controlled via the Benjamini/Hochberg method, setting a significance threshold at FDR < 0.05.
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The meta-analysis identified 5109 DEGs, with 2710 upregulated and 2399 downregulated genes, significantly more than the 120 DEGs shared across the five studies.
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The meta-analysis identified 5109 DEGs, with 2710 upregulated and 2399 downregulated genes, significantly more than the 120 DEGs shared across the five studies.
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After categorizing genes from the GEO datasets into AA or control groups, a random-effects model incorporating an effect-size approach was used to manage batch effects and harmonize data across studies. Z-scores derived from p values were crucial for evaluating the consistency and scale of gene expression variations. The false discovery rate (FDR) was controlled via the Benjamini/Hochberg method, setting a significance threshold at FDR < 0.05.
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{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40748556", "kind": "science-record", "revision": 2, "content_hash": "sha256:ea92c6aa36edb490bdcce3852d09ac4b9067992c45e84639a36d4a8893712cf4", "created_at": "2026-11-01T20:30:50Z", "updated_at": "2026-11-01T21:35:33Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Meta-Analysis of Gene Expression Reveals the Core Transcriptomic Profile of Lesional Scalp in Alopecia Areata.", "doi": "10.1007/s13555-025-01471-6", "pmid": "40748556", "authors": ["Irene Rivera-Ruiz", "Jesús Gay-Mimbrera", "Pedro J Gómez-Arias", "Macarena Aguilar-Luque", "Miguel Juan-Cencerrado", "Carmen Mochón-Jiménez", "Esmeralda Parra-Peralbo", "Beatriz Isla-Tejera", "Francisco Gómez-García", "Juan Ruano"], "journal": "Dermatology and therapy", "year": 2025, "abstract": "INTRODUCTION: Alopecia areata (AA) is an immune-mediated inflammatory skin disease that targets hair follicles. Current research yields varied lists of differentially expressed genes (DEGs). A meta-analytic approach is essential to consolidate these findings into a consistent tissue signature. This study aimed to perform a meta-analysis of gene expression datasets to establish a comprehensive molecular signature of AA lesional scalp.\nMETHODS: We conducted a meta-analysis of transcriptomic data from human studies on lesional skin gene expression in AA. Reanalyzing 132 samples (82 patients with AA and 50 controls) from five Gene Expression Omnibus (GEO) datasets (GSE68801, GSE45512, GSE80342, GSE58573, GSE74761), we employed an effect size approach within a random-effects model to identify unique and shared DEGs and enriched biological pathways. The protocol is registered in PROSPERO (CRD42024559847).\nRESULTS: The meta-analysis identified 5109 DEGs, with 2710 upregulated and 2399 downregulated genes, significantly more than the 120 DEGs shared across the five studies. Consistently expressed genes included CXCL9, CCL18, CXCL10, CD8A, and GZMB (FDR < 0.05). The analysis highlighted chemokines/receptors (CCL13, CCR1, XCL1) and markers of cytotoxic T lymphocytes (GZMA, GZMH, GZMK) and NK cells (NKG2A, NKG2D). Downregulated genes involved type I (KRT31-35, KRT38) and type II (KRT81-86) keratins and proteins crucial for hair follicle structure and function (PADI3, GPRC5D, DSG4, FGF18). Functional analysis showed enrichment in Th1, Th2, and Th17 pathways, particularly through JAK-STAT signaling (p < 0.01).\nCONCLUSION: This core transcriptome of AA lesions provides new insights into the disease's pathogenesis and identifies potential targets for treatment.", "claims": [{"id": "claim-method", "statement": "After categorizing genes from the GEO datasets into AA or control groups, a random-effects model incorporating an effect-size approach was used to manage batch effects and harmonize data across studies. Z-scores derived from p values were crucial for evaluating the consistency and scale of gene expression variations. The false discovery rate (FDR) was controlled via the Benjamini/Hochberg method, setting a significance threshold at FDR < 0.05.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40748556", "locator": "sections[6] \"Meta-Analysis\" paragraph 2", "quote": "After categorizing genes from the GEO datasets into AA or control groups, a random-effects model incorporating an effect-size approach was used to manage batch effects and harmonize data across studies. Z-scores derived from p values were crucial for evaluating the consistency and scale of gene expression variations. The false discovery rate (FDR) was controlled via the Benjamini/Hochberg method, setting a significance threshold at FDR < 0.05."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets analyzed during the current study are available in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) repository, and can be accessed through the following accession numbers: GSE68801, GSE45512, GSE80342, GSE58573, GSE74761, GSE111061. These public datasets were used under open access terms and can be freely accessed for further research. Additional data that support the findings of this study are available from the corresponding author upon reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40748556", "locator": "sections[25] \"notes\" paragraph 1", "quote": "The datasets analyzed during the current study are available in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) repository, and can be accessed through the following accession numbers: GSE68801, GSE45512, GSE80342, GSE58573, GSE74761, GSE111061. These public datasets were used under open access terms and can be freely accessed for further research. Additional data that support the findings of this study are available from the corresponding author upon reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The meta-analysis identified 5109 DEGs, with 2710 upregulated and 2399 downregulated genes, significantly more than the 120 DEGs shared across the five studies.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40748556", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "The meta-analysis identified 5109 DEGs, with 2710 upregulated and 2399 downregulated genes, significantly more than the 120 DEGs shared across the five studies."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The meta-analysis identified 5109 DEGs, with 2710 upregulated and 2399 downregulated genes, significantly more than the 120 DEGs shared across the five studies.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:40748556"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE45512"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE45512"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40748556", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1007/s13555-025-01471-6", "sha256": "sha256:1d5492b14f4fc82d033d43b41eff78aa624942282813eb60f3a068866c3dd69a", "bytes": 39346, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1007/s13555-025-01471-6", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12454715", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE45512", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE45512", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE45512", "version": null, "note": "The datasets analyzed during the current study are available in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) repository, and can be accessed through the following accession numbers: GSE68801, GSE45512, GSE80342, GSE58573, GSE74761, GSE111061. These public datasets were used under open access terms and can be freely accessed for further research. Additional data that support the findings of this study are available from the corresponding author upon reasonable request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets analyzed during the current study are available in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) repository, and can be accessed through the following accession numbers: GSE68801, GSE45512, GSE80342, GSE58573, GSE74761, GSE111061. These public datasets were used under open access terms and can be freely accessed for further research. Additional data that support the findings of this study are available from the corresponding author upon reasonable request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1105869", "GSM1105870", "GSM1105871", "GSM1105872", "GSM1105873", "GSM1105874", "GSM1105875", "GSM1105876", "GSM1105877", "GSM1105878"], "sample_count": 10, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Human Alopecia Areata Skin Profiling", "resolution_checked_at": "2026-11-01T20:16:08Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE58573", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE58573", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE58573", "version": null, "note": "The datasets analyzed during the current study are available in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) repository, and can be accessed through the following accession numbers: GSE68801, GSE45512, GSE80342, GSE58573, GSE74761, GSE111061. These public datasets were used under open access terms and can be freely accessed for further research. Additional data that support the findings of this study are available from the corresponding author upon reasonable request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets analyzed during the current study are available in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) repository, and can be accessed through the following accession numbers: GSE68801, GSE45512, GSE80342, GSE58573, GSE74761, GSE111061. These public datasets were used under open access terms and can be freely accessed for further research. Additional data that support the findings of this study are available from the corresponding author upon reasonable request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1414312", "GSM1414313", "GSM1414314", "GSM1414315", "GSM1414316", "GSM1414317", "GSM1414318"], "sample_count": 7, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "First ruxolitinib treatment of human alopecia areata patients", "resolution_checked_at": "2026-11-01T20:16:08Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE68801", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE68801", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE68801", "version": null, "note": "The datasets analyzed during the current study are available in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) repository, and can be accessed through the following accession numbers: GSE68801, GSE45512, GSE80342, GSE58573, GSE74761, GSE111061. 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