CPE overexpression is correlated with pelvic lymph node metastasis and poor prognosis in patients with early-stage cervical cancer

Shen, Hongwei; Tan, Jinfeng; Shang, Jianhong; Hou, Minzhi; Li, Jun; He, Li; Yao, Shuzhong; He, Shanyang

doi:10.1007/s00404-015-3985-6

Cited by 18 publications

(18 citation statements)

References 34 publications

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“…CPE may also have different effects on invasion and migration depending on the tumor type. In glioblastoma (GBM) cells, CPE has been identified as a regulator of RPS6 within the mTORc1 signaling pathway to reduce aerobic glycolysis and migration, which negatively affects tumor cell invasion and migration [20]; in contrast, CPE may promote migration and invasion in other tumor types such as cervical cancer and osteosarcoma [17, 21], although the underlying mechanism remains to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Yang

Chen

et al. 2019

Genes Cancer

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Carboxypeptidase E (CPE), a prohormone processing enzyme, is a 476- amino acid protein with a signal peptide in its N-terminus and is expressed in the nervous and the endocrine systems. Recent evidence indicate CPE plays various non-enzymatic roles in the endocrine and nervous systems and in various cancers. Besides wild type (WT) CPE, a 40-kDa CPE protein that localizes in the nucleus and cytoplasm has been described in embryonic mouse brain. In this study we have cloned this CPE variant encoding the 40kDa CPE-ΔN protein from human cancer cells. RACE assay and sequence analysis confirmed existence of this CPE variant mRNA, which has 198 nucleotides removed within the first exon and 589 nucleotides from the 3’-UTR, respectively, compared to WT-CPE mRNA. Bioinformatic analysis revealed that this CPE variant mRNA has a shortened open reading frame, which starts coding from the 3rd ATG relative to WT-CPE mRNA and encodes a 40kDa N-terminus truncated CPE protein. RT-PCR and Western blot analysis showed that 40kDa CPE-ΔN is expressed in multiple cancer cell lines and tumor tissues. Overexpression of this 40kDa CPE-ΔN variant up-regulated expression of multiple metastatic genes encompassing different signaling pathways, suggesting potentially an important role of CPE-ΔN in tumor metastasis.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Yang

Chen

et al. 2019

Genes Cancer

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“…CPE has been shown to be involved in tumorigenesis and cancer progression [5,6,7]. Clinical studies have demonstrated that elevated CPE mRNA and protein levels are correlated with poor prognosis in colorectal [8], hepatocellular carcinoma [9], and cervical cancer patients [10].…”

Section: Introductionmentioning

confidence: 99%

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

Hareendran

Yang

et al. 2019

IJMS

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Pancreatic cancer is one of the leading causes of cancer-related mortality worldwide. The molecular basis for the pathogenesis of this disease remains elusive. In this study, we have investigated the role of wild-type Carboxypeptidase E (CPE-WT) and a 40 kDa N-terminal truncated isoform, CPE-ΔN in promoting proliferation and invasion of Panc-1 cells, a pancreatic cancer cell line. Both CPE-WT and CPE-ΔN were expressed in Panc-1 and BXPC-3 pancreatic cancer cells. Immunocytochemical studies revealed that in CPE transfected Panc-1 cells, CPE-ΔN was found primarily in the nucleus, whereas CPE-WT was present exclusively in the cytoplasm as puncta, characteristic of secretory vesicles. Endogenous CPE-WT was secreted into the media. Overexpression of CPE-ΔN in Panc-1 cells resulted in enhancement of proliferation and invasion of these cells, as determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) cell proliferation assay and Matrigel invasion assay, respectively. In contrast, the expression of CPE-WT protein at comparable levels to CPE-ΔN in Panc-1 cells resulted in promotion of proliferation but not invasion. Importantly, there was an upregulation of the expression of CXCR2 mRNA and protein in Panc-1 cells overexpressing CPE-ΔN, and these cells exhibited significant increase in proliferation in a CXCR2-dependent manner. Thus, CPE-ΔN may play an important role in promoting pancreatic cancer growth and malignancy through upregulating the expression of the metastasis-related gene, CXCR2.

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“…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 ).…”

Section: Discussionmentioning

confidence: 99%

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

Qiu

Sun

et al. 2017

PeerJ

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BackgroundOral tongue squamous cell carcinoma (OTSCC) is the most common subtype of oral cancer. A predictive gene signature is necessary for prognosis of OTSCC.MethodsFive microarray data sets of OTSCC from the Gene Expression Omnibus (GEO) and one data set from The Cancer Genome Atlas (TCGA) were obtained. Differentially expressed genes (DEGs) of GEO data sets were identified by integrated analysis. The DEGs associated with prognosis were screened in the TCGA data set by univariate survival analysis to obtain a gene signature. A risk score was calculated as the summation of weighted expression levels with coefficients by Cox analysis. The signature was used to distinguish carcinoma, estimated by receiver operator characteristic curves and the area under the curve (AUC). All were validated in the GEO and TCGA data sets.ResultsIntegrated analysis of GEO data sets revealed 300 DEGs. A 16-gene signature and a risk score were developed after survival analysis. The risk score was effective to stratify patients into high-risk and low-risk groups in the TCGA data set (P < 0.001). The 16-gene signature was valid to distinguish the carcinoma from normal samples (AUC 0.872, P < 0.001).DiscussionWe identified a useful 16-gene signature for prognosis of OTSCC patients, which could be applied to clinical practice. Further studies were needed to prove the findings.

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CPE overexpression is correlated with pelvic lymph node metastasis and poor prognosis in patients with early-stage cervical cancer

Abstract: High-level CPE expression was associated with a poor prognosis in early-stage cervical cancer. CPE may serve as a biomarker for predicting PLNM and survival in these patients.

Cited by 18 publications

References 34 publications

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

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

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

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

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