Division of Transplantation, Department of Surgery, University of Virginia School of Medicine, Charlottesville, VA 22908-0679, USA.
Transplantation. 2012 Oct 27;94(8):851-8. doi: 10.1097/TP.0b013e318263702b.
The increased disparity between organ supply and need has led to the use of extended criteria donors and donation after cardiac death donors with other comorbidities.
We have examined the preimplantation transcriptome of 112 kidney transplant recipient samples from 100 deceased-donor kidneys by microarray profiling. Subject groups were segregated based on estimated glomerular filtration rate (eGFR) at 1 month after transplantation: the GFR-high group (n=74) included patients with eGFR 45 mL/min per 1.73 m(2), whereas the GFR-low group (n=35) included patients with eGFR 45 mL/min or less per 1.73 m(2).
Gene expression profiling identified higher expression of 160 probe sets (140 genes) in the GFR-low group, whereas expression of 37 probe sets (33 genes) was higher in the GFR-high group (P<0.01, false discovery rate <0.2). Four genes (CCL5, CXCR4, ITGB2, and EGF) were selected based on fold change and P value and further validated using an independent set of samples. A random forest analysis identified three of these genes (CCL5, CXCR4, and ITGB2) as important predictors of graft function after transplantation.
Inclusion of pretransplantation molecular gene expression profiles in donor quality assessment systems may provide the necessary information for better donor organ selection and function prediction. These biomarkers would further allow a more objective and complete assessment of procured renal allografts at pretransplantation time.
通过微阵列分析，研究了 100 例死亡供体 112 例肾移植受者样本的植入前转录组。根据移植后 1 个月时的肾小球滤过率（estimated glomerular filtration rate，eGFR）将受者分为两组：GFR-高组（n=74）包括 eGFR 45 mL/min/1.73 m 2 的患者，GFR-低组（n=35）包括 eGFR 45 mL/min/1.73 m 2 或更低的患者。
我们通过微阵列分析，研究了 100 例死亡供体的 112 例肾移植受者样本的植入前转录组。根据移植后 1 个月时的肾小球滤过率（estimated glomerular filtration rate，eGFR）将受者分为两组：GFR-高组（n=74）包括 eGFR 45 mL/min/1.73 m 2 的患者，GFR-低组（n=35）包括 eGFR 45 mL/min/1.73 m 2 或更低的患者。
基因表达谱分析发现，GFR-低组有 160 个探针集（140 个基因）的表达较高，而 GFR-高组有 37 个探针集（33 个基因）的表达较高（P<0.01，假发现率<0.2）。根据 fold change 和 P 值选择了 4 个基因（CCL5、CXCR4、ITGB2 和 EGF），并使用独立样本进行了进一步验证。随机森林分析确定了这 3 个基因（CCL5、CXCR4 和 ITGB2）是移植后移植物功能的重要预测因子。
将移植前分子基因表达谱纳入供体质量评估系统，可能为更好的供体器官选择和功能预测提供必要的信息。这些生物标志物将进一步允许在移植前时间对获取的肾同种异体移植物进行更客观和完整的评估。
