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

Tumour Biol. 2016 Jul;37(7):9745-53. doi: 10.1007/s13277-016-4814-7. Epub 2016 Jan 23.


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.

Keywords: Biomarker; Carboxypeptidase E; Hepatocellular carcinoma; Overall survival; Recurrence-free survival.

Publication types

  • Comparative Study

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Carboxypeptidase H / genetics*
  • Carcinoma, Hepatocellular / enzymology
  • Carcinoma, Hepatocellular / pathology*
  • Carcinoma, Hepatocellular / surgery
  • Follow-Up Studies
  • Humans
  • Liver / metabolism*
  • Liver / pathology
  • Liver Neoplasms / enzymology
  • Liver Neoplasms / pathology*
  • Liver Neoplasms / surgery
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local / diagnosis*
  • Neoplasm Recurrence, Local / enzymology
  • Neoplasm Recurrence, Local / surgery
  • Neoplasm Staging
  • Prognosis
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction


  • Biomarkers, Tumor
  • RNA, Messenger
  • Carboxypeptidase H