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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: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.

Project description:Pancreatic cancer (PC) is a stubborn malignancy with high lethality and a low 5-year overall survival (OS) rate. Collagen type VII α1 chain (COL7A1), a major component of the extracellular matrix, serves important roles in numerous physiological processes and various illnesses. COL7A1 protein acts as an anchoring fibril between the external epithelial cells and the underlying stroma, and mutation of COL7A1 could cause recessive dystrophic epidermolysis bullosa. Raw data for PC were acquired from The Cancer Genome Atlas and the Gene Expression Omnibus database, and raw data for the normal pancreas were obtained from the Genotype-Tissue Expression database. COL7A1 mRNA expression in PC tissues was compared with that in either paired (GSE15471 dataset) or unpaired (all other data) normal pancreas tissues. The association between COL7A1 mRNA expression and clinicopathological factors was assessed using logistic regression analysis. Cox analysis and Kaplan-Meier analysis were used to evaluate the role of COL7A1 mRNA expression in prognosis and nomograms were constructed. Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis, Gene Set Enrichment Analysis (GSEA) and single-sample GSEA (ssGSEA) were performed to evaluate the relevant functions of COL7A1 and correlation with immune cell infiltration. Furthermore, reverse transcription-quantitative PCR was used to assess the mRNA expression levels of COL7A1 in PC. The present study demonstrated that COL7A1 mRNA expression was higher in PC tissues compared with in normal pancreas tissues. The Kaplan-Meier survival analysis indicated that patients with PC with high COL7A1 mRNA expression had shorter overall survival (OS), disease-specific survival (DSS) and progression-free interval (PFI) times compared with patients with PC with low COL7A1 mRNA expression. Multivariate analysis demonstrated that COL7A1 mRNA expression was an independent risk factor for OS, DSS and PFI. Nomogram and calibration plots were constructed to predict the prognosis of patients with PC. GSEA demonstrated that high mRNA expression levels of COL7A1 were associated with multiple cancer-related pathways. ssGSEA analysis indicated that COL7A1 expression was positively associated with natural killer CD56bright cells and T helper (Th)2 cells, and negatively associated with Th17 cells and eosinophils. The results of the present study suggested that COL7A1 could be an independent biomarker and an influential moderator of immune infiltration in PC.

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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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