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The Road to Tolerance: Molecular Biomarkers for Prediction and Diagnosis of Post-transplant Complications in Liver Transplantation

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Immunology".

Deadline for manuscript submissions: 30 May 2024 | Viewed by 1770

Special Issue Editor


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Guest Editor
1. Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Taoyuan, Taiwan
2. Liver Transplantation Center, Kaohsiung Chang Gung Memotial Hospital, Kaohsiung, Taiwan
Interests: transplant immunology; liver biology; biomarker discovery; photobiomodulation
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Special Issue Information

Dear Colleagues,

Liver transplantation is widely accepted as an effective therapeutic modality for end-stage liver diseases. The results of liver transplantation have improved due to the improvement of perioperative techniques and the introduction of immunosuppressive drugs. However, post-transplant complications are common in the early and long-term period and contribute to significant morbidity and mortality. Therefore, how we precisely predict/diagnose post-transplant complications such as early allograft dysfunction, biliary complications, infection, acute and chronic rejection, and disease recurrence (fatty liver/NASH, hepatitis, fibrosis, cirrhosis, or hepatocellular carcinoma) is a quite important issue for achieving the road to tolerance in liver transplantation. The scope of the Special Issue is to summarize potential biomarkers for prediction and diagnosis of post-transplant complications both in experimental and clinical liver transplantation, and we discuss the future perspectives for tolerance induction in liver transplantation. Original articles and comprehensive reviews in the topic that focus on molecular research are warmly welcomed.

Topics include but are not limited to:

  • Omics for biomarker discovery in liver transplantation;
  • Current and future diagnostic tools in liver transplantation;
  • Molecular mechanisms of rejection and tolerance in liver transplantation;
  • Molecular mechanisms of disease recurrence after liver transplantation;
  • Strategies for prevention of post-transplant complications in liver transplantation;
  • Strategies for tolerance induction in liver transplantation.

Dr. Toshiaki Nakano
Guest Editor

Manuscript Submission Information

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Keywords

  • acute rejection
  • animal models
  • biliary complications
  • chronic rejection
  • cirrhosis
  • fatty liver
  • fibrosis
  • hepatitis
  • hepatocellular carcinoma
  • jaundice
  • NASH
  • omics
  • tolerance
 

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Research

12 pages, 1449 KiB  
Article
Overexpression of miR-4669 Enhances Tumor Aggressiveness and Generates an Immunosuppressive Tumor Microenvironment in Hepatocellular Carcinoma: Its Clinical Value as a Predictive Biomarker
by Toshiaki Nakano, Chao-Long Chen, I-Hsuan Chen, Hui-Peng Tseng, Kuei-Chen Chiang, Chia-Yun Lai, Li-Wen Hsu, Shigeru Goto, Chih-Che Lin and Yu-Fan Cheng
Int. J. Mol. Sci. 2023, 24(9), 7908; https://doi.org/10.3390/ijms24097908 - 26 Apr 2023
Cited by 6 | Viewed by 1442
Abstract
Accumulating evidence suggests the involvement of tumor-derived exosomes in the development and recurrence of hepatocellular carcinoma (HCC). We previously identified miR-4669 as a highly expressed microRNA in circulating exosomes obtained from patients with post-transplant HCC recurrence. This study aimed to explore how overexpression [...] Read more.
Accumulating evidence suggests the involvement of tumor-derived exosomes in the development and recurrence of hepatocellular carcinoma (HCC). We previously identified miR-4669 as a highly expressed microRNA in circulating exosomes obtained from patients with post-transplant HCC recurrence. This study aimed to explore how overexpression of miR-4669 affects HCC development and recurrence. The impact of miR-4669 overexpression in Hep3B cells on tumor cell behavior and the tumor microenvironment was evaluated in vitro. In addition, the clinical value of exosomal miR-4669 for the prediction of treatment response to HCC downstaging therapies and following post-transplant HCC recurrence was explored. Overexpression of miR-4669 enhanced migration ability and led to acquired sorafenib resistance with an elevation of sirtuin 1 and long noncoding RNA associated with microvascular invasion. Active release of tumor-derived exosomes and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) contributed to generating an immunosuppressive tumor microenvironment through the induction of M2 macrophage polarization. The retrospective analysis demonstrated the clinical value of exosomal miR-4669 for predicting treatment response to HCC downstaging therapies and for risk assessment of post-transplant HCC recurrence. In summary, the present data demonstrate the impact of exosomal miR-4669 on HCC recurrence through the enhancement of tumor aggressiveness and generation of an immunosuppressive tumor microenvironment. Full article
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