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Long Non-coding RNA Expression Profiling in Biopsy to Identify Renal Allograft at Risk of Chronic Damage and Future Graft Loss

机译:活检中的长链非编码 RNA 表达谱分析,以识别有慢性损伤和未来移植物丢失风险的同种异体肾移植物

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The loss of allograft from chronic damage is still the major risk that renal transplant recipients face today. Biomarkers for early detection of chronic damage are needed to improve the long-term graft survival. This study aimed to identify long non-coding RNA (lncRNA) biomarkers associated with chronic damage and graft loss after renal transplantation. Gene Expression Omnibus (GEO) datasets including GSE57387 (n = 101), GSE21374 (n = 282), and GSE25902 (n = 24) from three high-quality studies were analyzed. By repurposing the publicly available array-based data coupled with Affymetrix Human Exon 1.0 ST and Human U133 Plus 2.0 arrays, we obtained expression profiles of 11323 and 3383 lncRNAs in biopsies after renal transplantation, respectively. The logistic regression model and Cox regression model were applied to identify lncRNAs associated with chronic damage and graft survival. High AC093673.5 expression was identified as significantly associated with the three endpoints including chronic damage, progressive chronic histological damage, and graft failure across these three datasets. A six-lncRNA signature was created to predict renal allograft at risk of chronic damage with a high predictive ability (AUC = 0.94). Gene set enrichment analysis (GSEA) indicated that our lncRNA signature was related with allograft rejection and immunity. Our study highlights the importance of lncRNAs in chronic graft damage and allograft loss, supporting their potential role as prognosis biomarkers.
机译:慢性损伤导致的同种异体移植物丢失仍然是肾移植受者今天面临的主要风险。需要用于早期检测慢性损伤的生物标志物来提高移植物的长期存活率。本研究旨在鉴定与肾移植后慢性损伤和移植物丢失相关的长链非编码RNA(lncRNA)生物标志物。分析了来自三项高质量研究的基因表达综合 (GEO) 数据集,包括 GSE57387 (n = 101)、GSE21374 (n = 282) 和 GSE25902 (n = 24)。通过重新利用公开可用的基于芯片的数据与 Affymetrix 人外显子 1.0 ST 和人 U133 Plus 2.0 阵列相结合,我们分别获得了肾移植后活检中 11323 和 3383 个 lncRNA 的表达谱。采用logistic回归模型和Cox回归模型鉴定与慢性损伤和移植物存活相关的lncRNA。在这三个数据集中,高 AC093673.5 表达被确定为与三个终点显着相关,包括慢性损伤、进行性慢性组织学损伤和移植失败。创建了一个六-lncRNA 特征来预测具有高预测能力 (AUC = 0.94) 的同种异体肾移植物有慢性损伤的风险。基因集富集分析(GSEA)表明,我们的lncRNA特征与同种异体移植排斥反应和免疫有关。我们的研究强调了lncRNA在慢性移植物损伤和同种异体移植物丢失中的重要性,支持它们作为预后生物标志物的潜在作用。

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