Department of Visceral, Transplant and Thoracic Surgery, Center of Operative Medicine, Medical University of Innsbruck, Innsbruck, Austria.
Institute of Bioinformatics, Biocenter, Medical University of Innsbruck, Innsbruck, Austria.
Front Immunol. 2021 Jul 20;12:606146. doi: 10.3389/fimmu.2021.606146. eCollection 2021.
In search for novel biomarkers to assess graft quality, we investigated whether defined candidate genes are predictive for outcome after liver transplantation (LT). Zero-hour liver biopsies were obtained from 88 livers. Gene expression of selected candidate markers was analyzed and correlated with clinical parameters as well as short and long-term outcomes post LT. Whereas both, the calculated Eurotransplant Donor-Risk-Index and the donor body mass index, had either a poor or no predictive value concerning serum levels indicative for liver function (ALT, AST, GGT, bilirubin) after 6 months, chronological donor age was weakly predictive for serum bilirubin (AUC=0.67). In contrast, the major histcompatibility complex class I related chain A (MICA) mRNA expression demonstrated a high predictive value for serum liver function parameters revealing an inverse correlation (e.g. for ALT: 3 months p=0.0332; 6 months p=0.007, 12 months 0.0256, 24 months p=0.0098, 36 months, p=0.0153) and proved significant also in a multivariate regression model. Importantly, high expression of MICA mRNA revealed to be associated with prolonged graft survival (p=0.024; log rank test) after 10 years of observation, whereas low expression was associated with the occurrence of death in patients with transplant related mortality (p=0.031). Given the observed correlation with short and long-term graft function, we suggest MICA as a biomarker for pre-transplant graft evaluation.
在寻找评估移植物质量的新型生物标志物的过程中,我们研究了候选基因是否可以预测肝移植(LT)后的结局。从 88 个肝脏中获取零时间肝脏活检。分析了选定候选标记物的基因表达,并将其与临床参数以及 LT 后的短期和长期结果相关联。虽然欧洲移植供体风险指数和供体体重指数的计算值都对 6 个月后的肝功能(ALT、AST、GGT、胆红素)指示血清水平的预测价值很差或没有预测价值,但供体的实际年龄与血清胆红素呈弱相关(AUC=0.67)。相比之下,主要组织相容性复合体 I 类相关链 A(MICA)mRNA 表达对血清肝功能参数具有较高的预测价值,显示出反相关(例如 ALT:3 个月 p=0.0332;6 个月 p=0.007,12 个月 p=0.0256,24 个月 p=0.0098,36 个月 p=0.0153),并且在多变量回归模型中也具有统计学意义。重要的是,MICA mRNA 的高表达与 10 年观察期后的延长移植物存活率相关(p=0.024;对数秩检验),而低表达与移植相关死亡率患者的死亡发生相关(p=0.031)。鉴于观察到与短期和长期移植物功能的相关性,我们建议 MICA 作为移植前移植物评估的生物标志物。