Department of Hepato-Pancreato-Biliary Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, China.
Department of Gastrointestinal Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Zhejiang, China.
J Immunol Res. 2022 Jun 17;2022:7212852. doi: 10.1155/2022/7212852. eCollection 2022.
Inflammation within areas of interstitial fibrosis and tubular atrophy (IF/TA) is associated with kidney allograft failure. The aim of this study was to reveal new diagnostic markers of IF/TA based on bioinformatics analysis.
Raw data of IF/TA samples after kidney transplantation and control samples after kidney transplantation were extracted from the Gene Expression Omnibus (GEO) database (GSE76882 and GSE120495 datasets), and genes that were differentially expressed between the two groups (DEGs) were screened. Gene Set Enrichment Analysis (GSEA), ESTIMATE and single sample GSEA (ssGSEA), least absolute shrinkage and selection operator (LASSO) regression analysis, and competing endogenous RNA (ceRNA) network were used to analyze the data.
The results of GSEA revealed that multiple immune-related pathways were enriched in the IF/TA group, and subsequent immune landscape analysis also showed that the IF/TA group had higher immune and stromal scores and up to 15 types of immune cells occupied them, such as B cells, cytotoxic cells, and T cells. LASSO regression analysis selected 6 (including , , , , , and ) out of 14 DE-IRGs as diagnostic genes to construct a diagnostic model. Then, receiver operating characteristic (ROC) curve analysis showed the powerful diagnostic value of the model, and the area under the curve (AUC) of a single diagnostic gene was greater than 0.75. The results of ingenuity pathway analysis (IPA) also indicated that DEGs were involved in the immune system and kidney disease-related pathways. Finally, we found multiple miRNAs that could regulate diagnostic genes from the ceRNA network.
This study identified 6 IF/TA-related genes, which might be used as a new diagnosis model in the clinical practice.
间质纤维化和肾小管萎缩（IF/TA）区域内的炎症与肾移植失败有关。本研究旨在通过生物信息学分析揭示基于 IF/TA 的新诊断标志物。
从基因表达综合数据库（GEO）（GSE76882 和 GSE120495 数据集）中提取肾移植后 IF/TA 样本和肾移植后对照样本的原始数据，并筛选两组间差异表达基因（DEGs）。采用基因集富集分析（GSEA）、ESTIMATE 和单样本 GSEA（ssGSEA）、最小绝对值收缩和选择算子（LASSO）回归分析以及竞争内源性 RNA（ceRNA）网络分析数据。
GSEA 结果表明，IF/TA 组中多个免疫相关途径被富集，随后的免疫景观分析也表明 IF/TA 组具有更高的免疫和基质评分，多达 15 种免疫细胞浸润其中，如 B 细胞、细胞毒性细胞和 T 细胞。LASSO 回归分析从 14 个 DE-IRGs 中选择 6 个（包括、、、、和）作为诊断基因构建诊断模型。然后，接收者操作特征（ROC）曲线分析显示该模型具有强大的诊断价值，单个诊断基因的曲线下面积（AUC）大于 0.75。通路分析（IPA）的结果也表明 DEGs 参与了免疫系统和肾脏疾病相关途径。最后，我们从 ceRNA 网络中发现了多个可以调节诊断基因的 miRNAs。
本研究鉴定了 6 个与 IF/TA 相关的基因，它们可能作为临床实践中的新诊断模型。
