Transcriptome Analysis of Acute Phase Liver Graft Injury in Liver Transplantation

被引:5
作者
Lee, Nikki P. [1 ,2 ]
Wu, Haiyang [3 ]
Ng, Kevin T. P. [1 ]
Luo, Ruibang [3 ]
Lam, Tak-Wah [3 ]
Lo, Chung-Mau [1 ,2 ]
Man, Kwan [1 ,2 ]
机构
[1] Univ Hong Kong, Dept Surg, Hong Kong, Hong Kong, Peoples R China
[2] Zhejiang Univ, Collaborat Innovat Ctr Diag & Treatment Infect Di, Hangzhou 310003, Zhejiang, Peoples R China
[3] Univ Hong Kong, Dept Comp Sci, Hong Kong, Hong Kong, Peoples R China
关键词
Liver transplantation; liver graft injury; intragraft gene expression profiles; cell adhesion molecules; CD274; HFE; HEPATIC IRON OVERLOAD; HEPATOCELLULAR-CARCINOMA; ADHESION MOLECULES; REPERFUSION INJURY; TUMOR RECURRENCE; ISCHEMIA; INVASIVENESS; INHIBITION; PD-1/PD-L1; TOLERANCE;
D O I
10.3390/biomedicines6020041
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background: Liver transplantation remains the treatment of choice for a selected group of hepatocellular carcinoma (HCC) patients. However, the long-term benefit is greatly hampered by post-transplant HCC recurrence. Our previous studies have identified liver graft injury as an acute phase event leading to post-transplant tumor recurrence. Methods: To re-examine this acute phase event at the molecular level and in an unbiased way, RNA sequencing (RNA-Seq) was performed on liver graft biopsies obtained from the transplant recipients two hours after portal vein reperfusion with an aim to capture frequently altered pathways that account for post-transplant tumor recurrence. Liver grafts from recurrent recipients (n = 6) were sequenced and compared with those from recipients without recurrence (n = 5). Results: RNA expression profiles comparison pointed to several frequently altered pathways, among which pathways related to cell adhesion molecules were the most involved. Subsequent validation using quantitative polymerase chain reaction confirmed the differential involvement of two cell adhesion molecules HFE (hemochromatosis) and CD274 and their related molecules in the acute phase event. Conclusion: This whole transcriptome strategy unravels the molecular landscape of liver graft gene expression alterations, which can identify key pathways and genes that are involved in acute phase liver graft injury that may lead to post-transplant tumor recurrence.
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页数:9
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