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

IF 4.2 3区医学 Q1 DERMATOLOGY

Dermatology and Therapy Pub Date : 2025-10-01 Epub Date: 2025-08-01 DOI:10.1007/s13555-025-01471-6

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

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引用次数: 0

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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基因表达的荟萃分析揭示了斑秃病变头皮的核心转录组学特征。

简介：斑秃（AA）是一种以毛囊为靶点的免疫介导的炎症性皮肤病。目前的研究产生了不同的差异表达基因（DEGs）列表。荟萃分析方法是必要的，以巩固这些发现到一致的组织特征。本研究旨在对基因表达数据集进行荟萃分析，以建立头皮AA病变的综合分子特征。方法：我们对AA患者皮肤病变基因表达的转录组学数据进行了荟萃分析。我们重新分析了来自5个基因表达Omnibus （GEO）数据集（GSE68801、GSE45512、GSE80342、GSE58573、GSE74761）的132个样本（82例AA患者和50例对照），采用随机效应模型中的效应大小方法来识别独特和共享的deg和丰富的生物学途径。该协议在PROSPERO （CRD42024559847）中注册。结果：荟萃分析确定了5109个deg，其中2710个基因上调，2399个基因下调，显著高于5项研究共有的120个deg。一致表达的基因包括CXCL9、CCL18、CXCL10、CD8A和GZMB （FDR）。结论：这一AA病变的核心转录组为了解该疾病的发病机制和确定潜在的治疗靶点提供了新的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Dermatology and Therapy Medicine-Dermatology

CiteScore

6.00

自引率

8.80%

发文量

187

审稿时长

6 weeks

期刊介绍： Dermatology and Therapy is an international, open access, peer-reviewed, rapid publication journal (peer review in 2 weeks, published 3–4 weeks from acceptance). The journal is dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of dermatological therapies. Studies relating to diagnosis, pharmacoeconomics, public health and epidemiology, quality of life, and patient care, management, and education are also encouraged. Areas of focus include, but are not limited to all clinical aspects of dermatology, such as skin pharmacology; skin development and aging; prevention, diagnosis, and management of skin disorders and melanomas; research into dermal structures and pathology; and all areas of aesthetic dermatology, including skin maintenance, dermatological surgery, and lasers. The journal is of interest to a broad audience of pharmaceutical and healthcare professionals and publishes original research, reviews, case reports/case series, trial protocols, and short communications. Dermatology and Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an International and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of quality research, which may be considered of insufficient interest by other journals. The journal appeals to a global audience and receives submissions from all over the world.