N-terminal truncated carboxypeptidase E expression is associated with poor prognosis of lung adenocarcinoma

Abstract

Abstract. Lung cancer is a malignant tumor with high morbidity and mortality rates. To date, no suitable molecular diagnostic tool to predict disease recurrence and metastasis has been identified. The current study aimed to evaluate the potential of N-terminal truncated carboxypeptidase E (CPEΔN) to predict the recurrence and metastasis of lung adenocarcinoma. Western blotting revealed the co-expression of CPE and CPEΔN in the surgically collected pathological and pericarcinoma tissues tissues of 62.1% (59/95) lung adenocarcinoma patients. The full length CPE protein was predominantly expressed in pericarcinoma tissues and CPEΔN expression was identified in the pericarcinoma normal tissues of only 5.26% (5/95) patients. The 3-year postoperative recurrence and metastasis rates were significantly higher in patients with positive CPEΔN expression than in patients with negative CPEΔN expression (P=0.009). Furthermore, the overall survival rate of patients with predominant nuclear CPE expression was lower than that of patients with predominant cytoplasmic CPE expression (46.3 vs. 64.7%); however, no statistically significant difference was identified (P=0.125). Thus, the results of the current study indicated that CPEΔN may present a novel molecular biomarker for predicting recurrence and metastasis of lung adenocarcinoma, which may aid with stratifying patients by risk and thus, may facilitate individualized therapy.

Carboxypeptidase E-∆N Promotes Proliferation and Invasion of Pancreatic Cancer Cells via Upregulation of CXCR2 Gene Expression

“…Multivariate Cox regression analysis revealed that CPE-∆N expression was associated with lymph node and distant metastasis. Patients having CPE-∆N expression exhibited higher 3-year postoperative recurrence and metastasis rates than patients lacking CPE-∆N expression [20]. Enhanced CPE expression was documented in colorectal cancer (CRC) cell lines and patient tumor samples.…”

“…Overexpression of the 40 kDa CPE-ΔN in HCC cells upregulated the expression of metastasis-related genes, including chemokine receptor CXCR2, which is associated with PC malignancy [16,17,18,19]. Elevated tumor expression of CPE-ΔN protein has been correlated with poor prognosis in lung adenocarcinoma patients [20]. Additionally, overexpression of a 46 kDa CPE-ΔN isoform in osteosarcoma (OS) cells resulted in enhanced cell growth, migration, and invasion [21].…”

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

“…This CPE-ΔN variant acts in the nucleus to promote mouse embryonic cortical neuronal survival through up-regulation of expression of many genes that promote proliferation, differentiation, axonal guidance and cell migration, as well as programmed cell death, all events that take place during the formation of the nervous system [22]. 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.…”

“…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.…”

lncRNA FLVCR1‐AS1 silencing inhibits lung cancer cell proliferation, migration, and invasion by inhibiting the activity of the Wnt/β‐catenin signaling pathway

“…Lung cancer is a kind of malignant tumor with extremely high morbidity and mortality, which poses a great threat to human health and life . According to statistics, the 5‐year survival rate of patients with lung cancer has not improved significantly over the years .…”