Session Name: Biomarkers, Immune Assessment and Clinical Outcomes
Session Date & Time: None. Available on demand.
*Purpose: Chronic allograft injury (CAI) following kidney transplantation is still a threat to the allograft long-term survival. This study was designed to explore and analyze the data extracted from GEO (Gene Expression Omnibus) database and sort out the identification of allograft prognosis of kidney tranplanted patients by transcriptome.
*Methods: Three high quality arrays from GEO database, GSE25902 (n =24), GSE57387 (n =86) and GSE21374 (n =282), were obtained, which contained the whole transcriptome sequencing information of allograft biopsies within one year. Differential expressed genes (DEGs) were selected in common from GSE25902 and GSE57387 arrays. Then, the univariate and multivariate Cox regression model identified the independent graft-prognostic genes and a graft-prognostic index (PI). The diagnostic efficacy of this PI was validated by GSE21374 array. Finally, gene set enrichment analysis (GSEA) and Cibersort analysis were performed to screen key enriched pathways and biological process.
*Results: A total of 41 DEGs were identified and four DEGs, including ABI3BP, PALMD, TW4SF18, and WFDC, were selected as prognostic genes for allograft survival. A PI containing these four prognostic genes was established and good test power was validated in GSE21374 array. Moreover, the PI was found to be related with the occurrence of acute rejection, enriched in graft-associated and immune-associated biological processes or pathways, as well as in Wnt/beta-catenin pathway, which was confirmed by immunofluorescence in tissues from kidney transplanted recipients with CAI. In addition, The Cibersort analysis suggested macrophage polarization as a crucial mediator during CAI.
*Conclusions: We analyzed transcriptome data from three GSE arrays and established a graft-prognostic index, which showed a good test power to predict the allograft survival following renal transplant. This PI was also suggested to be correlated with a variety of immune-related biological processes and signaling, especially the Wnt/beta-catenin pathway, and macrophage polarization may contribute to the pathogenesis of CAI.
To cite this abstract in AMA style:Zhang X, Wang Z, Han Z, Tao J, Ju X, Tan R, Gu M. Identification and Validation of a Prognostic Index for Renal Allograft Survival Based on the Geo Database [abstract]. Am J Transplant. 2021; 21 (suppl 3). https://atcmeetingabstracts.com/abstract/identification-and-validation-of-a-prognostic-index-for-renal-allograft-survival-based-on-the-geo-database/. Accessed January 21, 2022.
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