Jia Junjun, Nie Yu, Geng Lei, Li Jianhui, Liu Jimin, Peng Yifan, Huang Junjie, Xie Haiyang, Zhou Lin, Zheng Shu-Sen
Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, First Affiliated Hospital, School of Medicine, Zhejiang University, College of Medicine, Hangzhou 310003, China.
Key Laboratory of Combined Multi-organ Transplantation, Ministry of Public Health, Hangzhou 310003, China.
Ann Transl Med. 2020 Mar;8(5):221. doi: 10.21037/atm.2020.01.59.
Liver transplantation (LT) is the most effective treatment for patients with end-stage liver diseases, but acute rejection is still a major concern. However, the mechanisms underlying rejection remain unclear. Biomarkers are lacking for predicting rejection and long-term survival after LT.
Isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomics was performed between acute cellular rejection (ACR) and non-rejection recipients. The molecular signature differences and potential biomarkers were identified by comprehensive bioinformatics. Heme oxygenase-1 (HO-1) expression and its association with clinical outcomes were investigated by tissue microarrays consisted of liver specimens from recipients with (n=80) and without ACR (n=57).
A total of 287 differentially expressed proteins (DEPs) were identified. Pathway analysis revealed that T/B cell activation, integrin/inflammation signaling pathway, etc. were significantly correlated with ACR. Through comprehensive bioinformatics, HO-1 was identified as a candidate potential biomarker for ACR. In tissue microarray (TMA) analysis, HO-1 expression was significantly higher in ACR group than in non-rejection group (P<0.01). Preoperative Child-Pugh and Meld scores were significantly higher in recipients with high HO-1 expression (P<0.01). In a mean 5-year follow-up, recipients with high HO-1 expression were associated with a shorter overall survival (P<0.05). Further multivariate analyses indicated that HO-1 could be an independent adverse prognostic factor for post-transplant survival (P=0.005).
A total of 287 DEPs were identified, providing a set of targets for further research. Recipients with high preoperative HO-1 expression were associated with ACR. HO-1 may be used as a potential biomarker for predicting the development of post-transplant allograft ACR and recipient's survival.
肝移植（LT）是终末期肝病患者最有效的治疗方法，但急性排斥反应仍是一个主要问题。然而，排斥反应的潜在机制仍不清楚。缺乏用于预测肝移植后排斥反应和长期生存的生物标志物。
在急性细胞排斥反应（ACR）患者和非排斥反应受者之间进行基于相对和绝对定量的等压标签（iTRAQ）蛋白质组学分析。通过综合生物信息学确定分子特征差异和潜在的生物标志物。采用由有（n = 80）和无ACR（n = 57）的受者肝脏标本组成的组织微阵列，研究血红素加氧酶-1（HO-1）的表达及其与临床结局的关系。
共鉴定出287种差异表达蛋白（DEP）。通路分析显示，T/B细胞活化、整合素/炎症信号通路等与ACR显著相关。通过综合生物信息学，HO-1被确定为ACR的候选潜在生物标志物。在组织微阵列（TMA）分析中，ACR组中HO-1的表达明显高于非排斥组（P<0.01）。HO-1高表达的受者术前Child-Pugh和Meld评分明显更高（P<0.01）。在平均5年的随访中，HO-1高表达的受者总生存期较短（P<0.05）。进一步的多因素分析表明，HO-1可能是移植后生存的独立不良预后因素（P = 0.005）。
共鉴定出287种DEP，为进一步研究提供了一系列靶点。术前HO-1高表达的受者与ACR相关。HO-1可作为预测移植后同种异体移植物ACR发生和受者生存的潜在生物标志物。
