Exploring hypoxia-related genes in spinal cord injury: a pathway to new therapeutic targets.

IF 3.5 3区医学 Q2 NEUROSCIENCES

Frontiers in Molecular Neuroscience Pub Date : 2025-05-20 eCollection Date: 2025-01-01 DOI:10.3389/fnmol.2025.1565430

Shihuan Cheng, Le Li, Mengmeng Xu, Ningyi Ma, Yinhua Zheng

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引用次数: 0

Abstract

Introduction: Spinal cord injury (SCI) remains a debilitating condition with limited therapeutic options. Exploring hypoxia-related genes in SCI may reveal potential therapeutic targets and improve our understanding of its pathogenesis.

Methods: We developed a diagnostic model using LASSO regression and Random Forest algorithms to investigate hypoxia-related genes in SCI. The model identified critical biomarkers by analyzing differentially expressed genes (DEGs) and hypoxia-related DEGs (HRDEGs). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), and Gene Set Variation Analysis (GSVA) were conducted to explore the biological roles of HRDEGs. The model's accuracy was validated using receiver operating characteristic curves, calibration plots, decision curves, and qPCR experiments.

Results: The diagnostic model identified Casp6, Pkm, Cxcr4, and Hexa as critical biomarkers among 186 HRDEGs out of 9,732 altered genes in SCI. These biomarkers were significantly associated with SCI pathogenesis. GO and KEGG analyses highlighted their roles in hypoxia responses, particularly through the hypoxia-inducible factor 1 pathway. The model demonstrated high accuracy, with an area under the curve exceeding 0.9. GSEA and GSVA revealed distinct pathways in low- and high-risk SCI groups, suggesting potential clinical stratification strategies.

Discussion: This study constructed a diagnostic model that confirmed Casp6, Pkm, Cxcr4, and Hexa as important biomarkers for SCI. The findings provide valuable insights into SCI pathogenesis and pave the way for novel treatment strategies. The integration of multi-omics data and comprehensive bioinformatics analyses offers a robust framework for identifying therapeutic targets and improving patient outcomes.

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探索缺氧相关基因在脊髓损伤：一个新的治疗靶点途径。

简介：脊髓损伤（SCI）仍然是一种使人衰弱的疾病，治疗选择有限。探索脊髓损伤的缺氧相关基因可能揭示潜在的治疗靶点，并提高我们对其发病机制的理解。方法：利用LASSO回归和随机森林算法建立诊断模型，研究脊髓损伤中缺氧相关基因。该模型通过分析差异表达基因（DEGs）和缺氧相关DEGs （HRDEGs）来识别关键生物标志物。通过基因本体（GO）、京都基因与基因组百科全书（KEGG）、基因集富集分析（GSEA）和基因集变异分析（GSVA）来探讨hrdeg的生物学作用。通过受试者工作特征曲线、校准图、决策曲线和qPCR实验验证了模型的准确性。结果：该诊断模型在脊髓损伤9,732个改变基因中的186个hrdeg中鉴定出Casp6、Pkm、Cxcr4和Hexa是关键的生物标志物。这些生物标志物与脊髓损伤发病机制显著相关。GO和KEGG分析强调了它们在缺氧反应中的作用，特别是通过缺氧诱导因子1途径。该模型具有较高的精度，曲线下面积超过0.9。GSEA和GSVA在低、高风险SCI组中显示了不同的通路，提示了潜在的临床分层策略。讨论：本研究构建了一个诊断模型，证实Casp6、Pkm、Cxcr4和Hexa是脊髓损伤的重要生物标志物。这些发现为脊髓损伤的发病机制提供了有价值的见解，并为新的治疗策略铺平了道路。多组学数据和综合生物信息学分析的整合为确定治疗靶点和改善患者预后提供了一个强大的框架。

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 Neuroscience NEUROSCIENCES-

CiteScore

5.70

自引率

2.10%

发文量

669

审稿时长

14 weeks

期刊介绍： Frontiers in Molecular Neuroscience is a first-tier electronic journal devoted to identifying key molecules, as well as their functions and interactions, that underlie the structure, design and function of the brain across all levels. The scope of our journal encompasses synaptic and cellular proteins, coding and non-coding RNA, and molecular mechanisms regulating cellular and dendritic RNA translation. In recent years, a plethora of new cellular and synaptic players have been identified from reduced systems, such as neuronal cultures, but the relevance of these molecules in terms of cellular and synaptic function and plasticity in the living brain and its circuits has not been validated. The effects of spine growth and density observed using gene products identified from in vitro work are frequently not reproduced in vivo. Our journal is particularly interested in studies on genetically engineered model organisms (C. elegans, Drosophila, mouse), in which alterations in key molecules underlying cellular and synaptic function and plasticity produce defined anatomical, physiological and behavioral changes. In the mouse, genetic alterations limited to particular neural circuits (olfactory bulb, motor cortex, cortical layers, hippocampal subfields, cerebellum), preferably regulated in time and on demand, are of special interest, as they sidestep potential compensatory developmental effects.