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ISSN 在线: 2162-6502

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Correlating Transcriptional Networks to Acute Rejection in Human Kidney Transplant Biopsies

卷 29, 册 5, 2019, pp. 401-412
DOI: 10.1615/CritRevEukaryotGeneExpr.2019027763
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摘要

Acute rejection (AR) in kidney transplants remains a major cause of allograft failure. This study investigates the association between gene networks and AR in human kidney transplant biopsies with weighted gene co-expression network analysis (WGCNA). The gene expression profiles of 403 (training set) and 702 (validation set) kidney transplant patients' biopsies were analyzed. WGCNA was conducted, and 11 co-regulated gene modules were identified. Each module was investigated with a t-test for AR and survival analysis for graft loss. The association between modules and AR molecular subtypes was also evaluated. Three transcriptional gene modules were associated with AR and graft loss of kidney transplant. One module constitutes unregulated immune response genes in AR and is associated with shorter graft survival (HR = 4.22, p-value = 4.29 × 10−6). This module is more significantly up-regulated in T cell-mediated acute rejection (TCMR) than in non-TCMRs. Hub genes such as HLA-DMA, CORO1A, PYCARD, and CD53 were identified. The expression of the other two modules was down-regulated in AR patients and associated with a good graft prognosis (HR = 0.41 and 0.24, respectively). A systems biology network approach may help uncover gene networks in kidney transplant biopsies associated with AR and contribute to identifying new biomarkers.

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对本文的引用
  1. Teng Lisha, Shen Lingling, Zhao Wenjun, Wang Cuili, Feng Shi, Wang Yucheng, Bi Yan, Rong Song, Shushakova Nelli, Haller Hermann, Chen Jianghua, Jiang Hong, SLAMF8 Participates in Acute Renal Transplant Rejection via TLR4 Pathway on Pro-Inflammatory Macrophages, Frontiers in Immunology, 13, 2022. Crossref

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