Format

Send to

Choose Destination
J Transl Med. 2015 Dec 11;13:379. doi: 10.1186/s12967-015-0743-2.

HERC5 is a prognostic biomarker for post-liver transplant recurrent human hepatocellular carcinoma.

Author information

1
Department of Liver Surgery and Liver Transplantation, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 201203, China. fengxue6879@163.com.
2
Translational Bioinformatics, MedImmune, Gaithersburg, MD, 20878, USA. higgsb@medimmune.com.
3
Translational Bioinformatics, MedImmune, Gaithersburg, MD, 20878, USA. jiaqihuang94041@yahoo.com.
4
Translational Bioinformatics, MedImmune, Gaithersburg, MD, 20878, USA. morehousec@medimmune.com.
5
Translational Bioinformatics, MedImmune, Gaithersburg, MD, 20878, USA. weizhu365@gmail.com.
6
Translational Bioinformatics, MedImmune, Gaithersburg, MD, 20878, USA. yaox@medimmune.com.
7
Translational Bioinformatics, MedImmune, Gaithersburg, MD, 20878, USA. brohawnp@medimmune.com.
8
Translational Bioinformatics, MedImmune, Gaithersburg, MD, 20878, USA. xiaoz@medimmune.com.
9
Translational Bioinformatics, MedImmune, Gaithersburg, MD, 20878, USA. sebastiany@medimmune.com.
10
Translational Bioinformatics, MedImmune, Gaithersburg, MD, 20878, USA. zheng.r.liu@gmail.com.
11
Department of Liver Surgery and Liver Transplantation, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 201203, China. yunxia@163.com.
12
Translational Bioinformatics, MedImmune, Gaithersburg, MD, 20878, USA. shend@medimmune.com.
13
Translational Bioinformatics, MedImmune, Gaithersburg, MD, 20878, USA. kuzioram@medimmune.com.
14
Asia and Emerging Markets iMed, AstraZeneca R&D, 199 Liangjing Road, Shanghai, 201203, China. Harvey.Dong@astrazeneca.com.
15
Asia and Emerging Markets iMed, AstraZeneca R&D, 199 Liangjing Road, Shanghai, 201203, China. Hulin.Han@astrazeneca.com.
16
Asia and Emerging Markets iMed, AstraZeneca R&D, 199 Liangjing Road, Shanghai, 201203, China. Yi.Gu@astrazeneca.com.
17
Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 201203, China. nlorg@public.sta.net.cn.
18
Department of Liver Surgery and Liver Transplantation, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 201203, China. xiaqiang@medmail.com.cn.
19
Translational Bioinformatics, MedImmune, Gaithersburg, MD, 20878, USA. oliver_67@yahoo.com.

Abstract

BACKGROUND AND AIMS:

Orthotopic liver transplantation (OLT) can be an effective treatment option for certain patients with early stage hepatocellular carcinoma (HCC) meeting Milan, UCSF, or Hangzhou criteria. However, HCC recurrence rates post-OLT range from 20 to 40 %, with limited follow-up options. Elucidating genetic drivers common to primary and post-OLT recurrent tumors may further our understanding and help identify predictive biomarkers of recurrence-both to ultimately help manage clinical decisions for patients undergoing OLT.

METHODS:

Whole exome and RNA sequencing in matched primary and recurrent tumors, normal adjacent tissues, and blood from four Chinese HCC patients was conducted. SiRNA knockdown and both qRT-PCR and Western assays were performed on PLCPRF5, SNU449 and HEPG2 cell lines; immunohistochemistry and RNA Sequencing were conducted on the primary tumors of Chinese HCC patients who experienced tumor recurrence post-OLT (n = 9) or did not experience tumor recurrence (n = 12).

RESULTS:

In three independent HCC studies of patients undergoing transplantation (n = 21) or surgical resection (n = 242, n = 44) of primary tumors (total n = 307), HERC5 mRNA under-expression correlated with shorter: time to tumor recurrence (p = 0.007 and 0.02) and overall survival (p = 0.0063 and 0.023), even after adjustment for relevant clinical variables. HERC5 loss drives CCL20 mRNA and protein over-expression and associates with regulatory T cell infiltration as measured by FOXP3 expression. Further, matched primary and recurrent tumors from the 4 HCC patients indicated clonal selection advantage of Wnt signaling activation and CDKN2A inactivation.

CONCLUSIONS:

HERC5 plays a crucial role in HCC immune evasion and has clinical relevance as a reproducible prognostic marker for risk of tumor recurrence and survival in patients.

PMID:
26653219
PMCID:
PMC4676172
DOI:
10.1186/s12967-015-0743-2
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center