Analysis and validation of programmed cell death genes associated with spinal cord injury progression based on bioinformatics and machine learning

IF 4.8 2区医学 Q2 IMMUNOLOGY International immunopharmacology Pub Date : 2025-02-09 DOI:10.1016/j.intimp.2025.114220

Yongjie Wang , Zilin Zhang , Weiquan Gong , Zhenshan Lv , Jinwei Qi , Song Han , Boyuan Liu , Aijun Song , Zongyuan Yang , Longfei Duan , Shaokun Zhang

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引用次数: 0

Abstract

Background

Spinal cord injury (SCI) is a severe condition affecting the central nervous system. It is marked by a high disability rate and potential for death. Research has demonstrated that programmed cell death (PCD) plays a significant role in the death of neuronal cells during SCI. The objective of our work was to illustrate the significant contribution of PCD genes in the progression of SCI.

Methods

SCI-related datasets GSE5296, GSE47681, and GSE189070 from the Gene Expression Omnibus database were comprehensively analyzed using bioinformatics methods. Common differentially expressed genes were validated by post-intersection screening with PCD genes. We constructed a gene prediction model using the least absolute shrinkage and selection operator and the random forest algorithm to further screen for characteristic genes. We also performed Gene Ontology functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis and generated a protein–protein interaction network, analyzed immune cell infiltration, and predicted upstream miRNAs and transcription factors. In animal experiments, we performed immunofluorescence staining of mouse SCI regions to verify gene expression.

Results

A total of five characteristic genes (Ctsd, Abca1, Cst7, Ctsb, and Cybb) were identified in our study and showed excellent diagnostic efficacy in predicting SCI progression (areas under the curve values of the five characteristic genes were 0.976 for Ctsd, 0.993 for Abca1, 0.995 of Cst7,0.986 of Ctsb, 0.959 of Cybb). These characterized genes were highly expressed at the site of SCI. Immune cell infiltration analysis revealed that multiple immune cells were involved in SCI progression.

Conclusions

We identified five PCD genes (Ctsd, Abca1, Cst7, Ctsb, and Cybb) associated with SCI. This study helps to reveal the pathophysiologic influences of these genes on SCI and provides important insight for the development of more effective treatments.

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来源期刊

International immunopharmacology 医学-免疫学

CiteScore

8.40

自引率

3.60%

发文量

935

审稿时长

53 days

期刊介绍： International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.