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NCEH1 may be a prognostic biomarker for pancreatic cancer.

ABSTRACT: Neutral Cholesterol Ester Hydrolase 1 (NCEH1) is an enzyme involved in ether lipid metabolism, and the NCEH1 gene is overexpressed in a variety of tumors. However, its role in pancreatic cancer remains unknown. Therefore, we compared the gene transcription data of healthy and pancreatic cancer tissues using the Cancer Genome Atlas and Genotype-Tissue Expression databases. R software (v3.6.1) was used for the differential, clinicopathological correlation, and survival analyses. We found that NCEH1 was overexpressed in pancreatic cancer tissues compared with that in healthy tissues (P = 1.732 e-50), and that its expression level was related to lymph node metastasis. High NCEH1 expression was associated with poor overall survival (P = 0.002). Using univariate and multivariate Cox regression analyses, we determined that NCEH1 is an independent risk factor for pancreatic cancer. Gene set enrichment analysis identified that NCEH1 overexpression is prominent in cell-cell adhesion junctions, pancreatic cancer, cancer-associated pathways, prostate cancer, and chronic myeloid leukemia. In contrast, low NCEH1 expression correlated to high oxidative phosphorylation. Thus, we conclude that NCEH1 may be a prognostic biomarker for pancreatic cancer.

SUBMITTER: Lu Y

PROVIDER: S-EPMC7716126 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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NCEH1 may be a prognostic biomarker for pancreatic cancer.

Lu Yan Y Zhang Longyi L Chen Xuya X Zhang Qiaohong Q

International journal of clinical and experimental pathology 20201101 11

Neutral Cholesterol Ester Hydrolase 1 (NCEH1) is an enzyme involved in ether lipid metabolism, and the <i>NCEH1</i> gene is overexpressed in a variety of tumors. However, its role in pancreatic cancer remains unknown. Therefore, we compared the gene transcription data of healthy and pancreatic cancer tissues using the Cancer Genome Atlas and Genotype-Tissue Expression databases. R software (v3.6.1) was used for the differential, clinicopathological correlation, and survival analyses. We found th ...[more]

PMID: 33284889

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Project description:BackgroundUbiquitination is a basic post-translational modification of intracellular proteins and can be reversed enzymatically by DUBs (deubiquitinating enzymes). More than 90 DUBs have been identified. Among them, the deubiquitinating enzyme YOD1, a member of the ovarian tumor domain protease (OTUs) subfamily, is involved in the regulation of endoplasmic reticulum (ER)-related degradation pathways. In fact, it is reported that YOD1 is an important proliferation and metastasis-inducing gene, which can stimulate the characteristics of cancer stem cells and maintain circulating tumor cells (CTC). However, the expression level, prognostic effect and biological functional mechanism of YOD1 in pancreatic cancer are still unclear.ResultsIn the GEO and TCGA databases, YOD1 mRNA expression is significantly up regulated in a variety of human pancreatic cancer tissues. Survival analysis showed that the up regulation of YOD1 can predict poor prognosis of pancreatic cancer. Cox analysis showed that high YOD1 expression is an independent prognostic factor of pancreatic cancer. ROC analysis shows that YOD1 has significant diagnostic value. The immunohistochemistry (IHC) results showed that the protein expression level of YOD1 in pancreatic cancer tissue was higher than that in neighboring non-pancreatic cancer tissues (P < 0.001). In addition, we found that YOD1 expression is negatively correlated with the infiltration level of CD8 + T cells, macrophages, neutrophils and dendritic cells (DC) in pancreatic cancer. The expression of YOD1 has a strong correlation with the different immune marker sets in PAAD. Co-expression network and functional enrichment analysis indicate that YOD1 may participate in the development of pancreatic cancer through cell adhesion molecules, p53, Hippo, TGF-β and other pathways. The experimental results of EDU, Transwell, Immunohistochemistry (IHC), Western blot and Flow Cytometry indicate that YOD1 is highly expressed in pancreatic cancer cells and pancreatic cancer tissues, and its overexpression can promote the proliferation and metastasis of pancreatic cancer cells and affect the immune microenvironment.ConclusionOur results indicate that YOD1 may be a useful biomarker for the prognosis of human pancreatic cancer, and it may also be a potential molecular target for the diagnosis and treatment of pancreatic cancer.

Project description:Background: Alpha-enolase is an important glycolytic enzyme, and its aberrant expression has been associated with multiple tumor progression. However, few studies investigated the expression of alpha-enolase and its clinical significance in pancreatic cancer (PC). Objectives: To evaluate alpha-enolase level in PC tissues by immunohistochemical (IHC) analysis, and investigate the association of alpha-enolase expression with clinicopathologic features. Methods: The alpha-enolase levels in pancreatic cancer tissues were analyzed by using the Oncomine database. The expression of alpha-enolase, Ki67 and p53 in pancreatic cancer and adjacent normal tissues were evaluated by IHC using the corresponding primary antibodies on the commercial tissue arrays. We also examined their association with clinicopathologic parameters, and explored their prognostic value in PC. Results: We identified an elevation of alpha-enolase mRNA level in pancreatic cancer independent datasets from Oncomine. IHC analysis showed that alpha-enolase protein levels were elevated in 47% (n=100) PC tissue samples, but there was weak or no staining in the normal tissues. Statistical analysis revealed that high levels of alpha-enolase were significantly associated with Stage and Lymph node metastasis. Correlation analysis indicated that over-expression of alpha-enolase was positively associated with Ki67 expression and inversely correlated with p53 expression. Furthermore, membranous expression of alpha-enolase was also observed in 29.8% (14/47) total alpha-enolase positive samples, and was significantly associated with Lymph node metastasis. Kaplan-Meier survival analysis demonstrated that high total alpha-enolase expression was significantly associated with unfavorable survival, while membranous alpha-enolase expression was significantly associated with better survival of PC patients. Multivariate Cox analysis demonstrated that total alpha-enolase expression was an independent prognostic factor for PC patients. Conclusions: Our results suggested that alpha-enolase level was significantly elevated in pancreatic cancer tissues, which was closely associated with PC progression. It might be a candidate target for targeted pancreatic cancer treatments.

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NCEH1 may be a prognostic biomarker for pancreatic cancer.

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NCEH1 may be a prognostic biomarker for pancreatic cancer.

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