Table_1_A crucial exosome-related gene pair (AAMP and ABAT) is associated with inflammatory cells in intervertebral disc degeneration.docx

Identification of exosome-related genes (ERGs) and competing endogenous RNAs (ceRNAs) associated with intervertebral disc degeneration (IDD) may improve its diagnosis and reveal its underlying mechanisms. We downloaded 49 samples from Gene Expression Omnibus and identified candidate ERGs using differentially expressed ERGs (De-ERGs), exosome-related gene pairs (ERGPs), and machine learning algorithms [least absolute shrinkage and selection operator (LASSO) and support vector machine (SVM)]. Immune cell-related ERGs were selected via immune-infiltration analysis, and clinical values were assessed using receiver operating characteristic curves. Based on the De-ERGs, a ceRNA network comprising 1,512 links and 330 nodes was constructed and primarily related to signal transduction pathways, apoptosis-related biological processes, and multiple kinase-related molecular functions. In total, two crucial De-ERGs [angio-associated migratory cell protein (AAMP) and 4-aminobutyrate aminotransferase (ABAT)] were screened from results in De-ERGs, ERGPs, LASSO, and SVM. Increased AAMP expression and decreased ABAT expression were positively and negatively correlated with CD8+ T cell infiltration, respectively. AAMP/ABAT was the only pair differentially expressed in IDD and correlated with CD8+ T cell infiltration. Furthermore, AAMP/ABAT displayed higher accuracy in predicting IDD than individual genes. These results demonstrated the ERGP AAMP/ABAT as a robust signature for identifying IDD and associated with increased CD8+ T cell infiltration, suggesting it as a promising IDD biomarker.

鉴定与椎间盘退变（intervertebral disc degeneration, IDD）相关的外泌体相关基因（exosome-related genes, ERGs）及内源竞争RNA（competing endogenous RNAs, ceRNAs），可为该病的诊断提供优化思路并揭示其潜在发病机制。本研究从基因表达综合数据库（Gene Expression Omnibus）下载49例样本，通过差异表达外泌体相关基因（differentially expressed ERGs, De-ERGs）、外泌体相关基因对（exosome-related gene pairs, ERGPs）及机器学习算法[最小绝对收缩和选择算子（least absolute shrinkage and selection operator, LASSO）与支持向量机（support vector machine, SVM）]筛选候选外泌体相关基因；通过免疫浸润分析筛选与免疫细胞相关的外泌体相关基因，并采用受试者工作特征曲线（receiver operating characteristic curves）评估其临床价值。基于差异表达外泌体相关基因，本研究构建了包含1512条调控关联、330个节点的内源竞争RNA网络，该网络主要富集于信号转导通路、凋亡相关生物学过程及多种激酶相关分子功能。最终从差异表达外泌体相关基因、外泌体相关基因对、LASSO及SVM分析结果中，筛选得到2个关键差异表达外泌体相关基因：血管相关迁移细胞蛋白（angio-associated migratory cell protein, AAMP）与4-氨基丁酸氨基转移酶（4-aminobutyrate aminotransferase, ABAT）。AAMP表达上调与ABAT表达下调分别与CD8+ T细胞浸润呈正相关与负相关。AAMP/ABAT基因对是唯一在椎间盘退变中呈差异表达且与CD8+ T细胞浸润相关的基因对。此外，AAMP/ABAT基因对预测椎间盘退变的准确率高于单个基因。本研究结果表明，外泌体相关基因对AAMP/ABAT可作为识别椎间盘退变的可靠标志物，且与CD8+ T细胞浸润增加相关，提示其有望成为椎间盘退变的潜在生物标志物。