Identification and validation of five ferroptosis-related molecular signatures in keloids based on multiple transcriptome data analysis.

IF 3.9 3区生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Frontiers in Molecular Biosciences Pub Date : 2025-01-06 eCollection Date: 2024-01-01 DOI:10.3389/fmolb.2024.1490745

Zhen Sun, Yonghong Qin, Xuanfen Zhang

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引用次数: 0

Abstract

Introduction: Keloids are a common skin disorder characterized by excessive fibrous tissue proliferation, which can significantly impact patients' health. Ferroptosis, a form of regulated cell death, plays a crucial role in the development of fibrosis; however, its role in the mechanisms of keloid formation remains poorly understood.

Methods: This study aimed to identify key genes associated with ferroptosis in keloid formation. Data from the NCBI GEO database, including GSE145725, GSE7890, and GSE44270, were analyzed, comprising a total of 24 keloid and 17 normal skin samples. Additionally, single-cell data from GSE181316, which included 8 samples with complete expression profiles, were also evaluated. Differentially expressed genes were identified, and ferroptosis-related genes were extracted from the GeneCards database. LASSO regression was used to select key genes associated with keloids. Validation was performed using qRT-PCR and Western blot (WB) analysis on tissue samples from five keloid and five normal skin biopsies.

Results: A total of 471 differentially expressed genes were identified in the GSE145725 dataset, including 225 upregulated and 246 downregulated genes. Five ferroptosis-related genes were selected through gene intersection and LASSO regression. Two of these genes were upregulated, while three were downregulated in keloid tissue. Further analysis through GSEA pathway enrichment, GSVA gene set variation, immune cell infiltration analysis, and single-cell sequencing revealed that these genes were primarily involved in the fibrotic process. The qRT-PCR and WB results confirmed the expression patterns of these genes.

Discussion: This study provides novel insights into the molecular mechanisms of ferroptosis in keloid formation. The identified ferroptosis-related genes could serve as potential biomarkers or therapeutic targets for treating keloids.

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基于多转录组数据分析的瘢痕疙瘩中5个铁枯相关分子特征的鉴定和验证。

瘢痕疙瘩是一种常见的皮肤疾病，其特征是纤维组织过度增生，严重影响患者的健康。铁下垂是一种受调控的细胞死亡形式，在纤维化的发展中起着至关重要的作用；然而，其在瘢痕疙瘩形成机制中的作用仍然知之甚少。方法：本研究旨在鉴定与瘢痕疙瘩形成中铁下垂相关的关键基因。分析NCBI GEO数据库中的数据，包括GSE145725、GSE7890和GSE44270，共包括24份瘢痕疙瘩和17份正常皮肤样本。此外，还评估了来自GSE181316的单细胞数据，其中包括8个具有完整表达谱的样本。鉴定了差异表达基因，并从GeneCards数据库中提取了与铁枯病相关的基因。采用LASSO回归筛选与瘢痕疙瘩相关的关键基因。采用qRT-PCR和Western blot （WB）对5例瘢痕疙瘩和5例正常皮肤活检组织样本进行验证。结果：GSE145725数据集中共鉴定出471个差异表达基因，其中上调225个，下调246个。通过基因交叉和LASSO回归筛选出5个与嗜铁有关的基因。其中两个基因在瘢痕组织中上调，而三个基因在瘢痕组织中下调。通过GSEA通路富集、GSVA基因集变异、免疫细胞浸润分析和单细胞测序进一步分析发现，这些基因主要参与了纤维化过程。qRT-PCR和WB结果证实了这些基因的表达模式。讨论：本研究为瘢痕疙瘩形成中铁下垂的分子机制提供了新的见解。所鉴定的嗜铁相关基因可作为治疗瘢痕疙瘩的潜在生物标志物或治疗靶点。

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

Frontiers in Molecular Biosciences Biochemistry, Genetics and Molecular Biology-Biochemistry

CiteScore

7.20

自引率

4.00%

发文量

1361

审稿时长

14 weeks

期刊介绍： Much of contemporary investigation in the life sciences is devoted to the molecular-scale understanding of the relationships between genes and the environment — in particular, dynamic alterations in the levels, modifications, and interactions of cellular effectors, including proteins. Frontiers in Molecular Biosciences offers an international publication platform for basic as well as applied research; we encourage contributions spanning both established and emerging areas of biology. To this end, the journal draws from empirical disciplines such as structural biology, enzymology, biochemistry, and biophysics, capitalizing as well on the technological advancements that have enabled metabolomics and proteomics measurements in massively parallel throughput, and the development of robust and innovative computational biology strategies. We also recognize influences from medicine and technology, welcoming studies in molecular genetics, molecular diagnostics and therapeutics, and nanotechnology. Our ultimate objective is the comprehensive illustration of the molecular mechanisms regulating proteins, nucleic acids, carbohydrates, lipids, and small metabolites in organisms across all branches of life. In addition to interesting new findings, techniques, and applications, Frontiers in Molecular Biosciences will consider new testable hypotheses to inspire different perspectives and stimulate scientific dialogue. The integration of in silico, in vitro, and in vivo approaches will benefit endeavors across all domains of the life sciences.