Tumor Biology

, Volume 37, Issue 7, pp 9745–9753 | Cite as

Carboxypeptidase E is a prediction marker for tumor recurrence in early-stage hepatocellular carcinoma

  • Shiu-Feng Huang
  • Hong-Dar Isaac Wu
  • Ya-Ting Chen
  • Saravana R. K. Murthy
  • Yu-Ting Chiu
  • Yu Chang
  • Il-Chi Chang
  • Xuyu Yang
  • Y. Peng Loh
Original Article


Tumor recurrence and metastasis are the major causes of death for hepatocellular carcinoma (HCC) patients who are able to receive curative resection. Identifying the predicting biomarkers for tumor recurrence would improve their survival. RNA extracted from fresh frozen tumors and adjacent non-tumor liver tissues of 120 HCC patients were obtained from Taiwan Liver Cancer Network (TLCN) in year 2010 for determination of the carboxypeptidase E (CPE) expression level (including its splicing mutant CPE-ΔN) in the tumor tissue (T) and paired non-tumor liver tissue (N) by real-time quantitative polymerase chain reaction. All patients were male, had chronic hepatitis B virus infection, were in the early pathology stage, and received curative resection. The T/N ratio of the CPE expression level was correlated with the updated survival data from TLCN in 2015. The CPE expression level in the 120 HCC patients was divided into three groups according to the T/N ratio: <1, ≥1 and ≤2, and >2, respectively. By multivariate analyses, the recurrence-free survival (RFS) was only significantly associated with the pathology stage and the CPE expression level. For overall survival (OS), only the CPE expression level was the significant prognostic factor. The CPE expression level was also significantly correlated with the tumor recurrence for both stage I (p = 0.0106) and stage II patients (p = 0.0006). The CPE mRNA expression level in HCC can be a useful biomarker for predicting tumor recurrence in HCC patients who are in the early pathology stage and able to receive curative resection.


Carboxypeptidase E Hepatocellular carcinoma Recurrence-free survival Overall survival Biomarker 



Carboxypeptidase E


Hepatocellular carcinoma


Taiwan Liver Cancer Network


Tumor tissue


Paired non-tumor liver tissue


Recurrence-free survival


Overall survival


Alpha-fetal protein



We would like to thank Taiwan Liver Cancer Network (TLCN) for providing the liver tissue samples and related clinical data (all are anonymous) for our research. The tissue source is the five major medical centers in Taiwan: National Taiwan University Hospital, Chang Gung Memorial Hospital Linko, Taichung Veteran General Hospital, Chang Gung Memorial Hospital Kaohsiung, and Kaohsiung Veteran General Hospital. TLCN is supported by grants from the Ministry of Science and Technology (MOST 103-2325-B-182-011, MOST 104-2325-B-182-002) and National Health Research Institutes, Taiwan.

Compliance with ethical standards

The study protocol has been approved by the Institutional Review Board of National Health Research Institutes, Taiwan (NIRB EC0990701).

Financial support

This research was supported by grants from National Science Council (NSC-100-c-2320-400-012) and National Health Research Institutes (MG103-PP-004) to Dr. Shiu-Feng Huang and by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, USA (HD008804) to Dr. Y. Peng Loh.

Conflicts of interest



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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2016

Authors and Affiliations

  • Shiu-Feng Huang
    • 1
    • 2
  • Hong-Dar Isaac Wu
    • 3
  • Ya-Ting Chen
    • 1
  • Saravana R. K. Murthy
    • 4
  • Yu-Ting Chiu
    • 1
  • Yu Chang
    • 1
  • Il-Chi Chang
    • 1
  • Xuyu Yang
    • 4
  • Y. Peng Loh
    • 4
  1. 1.Institute of Molecular and Genomic MedicineNational Health Research InstitutesZhunaTaiwan
  2. 2.Department of Anatomical PathologyChung-Shan Medical University HospitalTaichungTaiwan
  3. 3.Department of Applied Mathematics and Institute of StatisticsNational Chung-Hsing UniversityTaichungTaiwan
  4. 4.Section on Cellular Neurobiology, Program on Developmental Neuroscience, Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institutes of HealthBethesdaUSA

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