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

Abstract

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.

A novel 40kDa N-terminal truncated carboxypeptidase E splice variant: cloning, cDNA sequence analysis and role in regulation of metastatic genes in human cancers

“…Aberrant expression of CPE has been found in several major tumors of epithelial origin, including lung, liver, colon, pancreatic and cervical cancers [13, 14, 15, 16, 17], as well as in neuroendocrine tumors such as insulinoma [3, 18], suggesting CPE might have a role in tumor progression. Evidences that CPE promotes tumor proliferation are emerging.…”

“…Similarly, CPE has been found in the nucleus as revealed by immunohistochemical (IHC) staining in some human cancers [21, 23]. Despite previous studies implicating the CPE variant induces proliferation and invasion in various tumor cell lines and to promote growth and metastasis of tumors in orthotopic models of nude mice, and could potentially be a biomarker in predicting metastasis and recurrence of cancer [13, 16, 23], the complete characterization of this CPE variant has not yet been carried out. In order to better understand the structure, regulation and biological function of this CPE-ΔN variant, we have now undertaken to clone and characterize the mRNA.…”

Integration of Breast Cancer Secretomes with Clinical Data Elucidates Potential Serum Markers for Disease Detection, Diagnosis, and Prognosis

“…Most importantly, each of the secreted proteins we identified with 20 or more SCs, except for CPE, has been detected in the serum of patients with different types of cancer ( Fig 7 ) and may be useful as markers for BC detection, disease recurrence and progression, or therapeutic intervention. Although CPE has not been detected in serum, it has been implicated as a marker of tumor growth, metastasis, and recurrence in hepatocellular carcinoma [ 103 ], pheochromocytomas, and many non-endocrine types of cancer [ 104 ]. It may be useful to screen blood for the proteins listed in Fig 7 for BC detection and classification of ERα-responsive (PIP and SERPINA3) and TNBC (LGALS3BP, SAA1, and TNC) tumors.…”

A 16-gene signature predicting prognosis of patients with oral tongue squamous cell carcinoma

“…CD69 is correlated with poor clinical outcomes and is confirmed to be an independent prognosticator for blood system tumors ( Del Poeta et al, 2012 ). CPE is a member of metallocarboxypeptidases family, and the CPE mRNA expression level can predict tumor recurrence in early-stage hepatocellular carcinoma, and predict poor prognosis in early-stage cervical cancer ( Huang et al, 2016b ; Shen et al, 2016 ). ITM2A is a poorly prognostic biomarker through inducing cell cycle arrest for ovarian cancer ( Nguyen et al, 2016 ).…”