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Integrated analysis of gene expression, alteration and clinical significance of carcinoembryonic antigen-related cell adhesion molecule 1 in cancer.

ABSTRACT: Even though cell-cell adhesion molecule carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is extensively studied since the discovery, the role of CEACAM1 in different cancers is not completely clarified. In the present study, we examined CEACAM1 expression and its association with patient survival in various cancers by analysis of multiple databases. Oncomine database analysis revealed that CEACAM1 expression was upregulated in lung and pancreatic cancers, but downregulated in colorectal and head and neck cancers. PrognoScan and Kaplan?Meier analyses showed that colorectal cancer patients as well as head and neck cancer patients with high CEACAM1 expression exhibited a higher overall survival rate. STRING analysis identified CEACAM3, CEACAM8, FN1, etc. as CEACAM1 interactors. Gene alteration analysis showed that CEACAM1 mutation predominantly occurred in the N-terminal. Coexpression analysis demonstrated that CEACAM1 had distinct coexpressed genes in different cancers, but KRT protein was consistently coexpressed with CEACAM1 in diverse cancer types. All the observations supported that CEACAM1 can serve as a diagnostic marker for some cancers, such as pancreatic cancer. And high CEACAM1 expression provides a better prognosis for some cancers, such as colorectal and head and neck cancers.

SUBMITTER: Weng CY

PROVIDER: S-EPMC7036084 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Integrated analysis of gene expression, alteration and clinical significance of carcinoembryonic antigen-related cell adhesion molecule 1 in cancer.

Weng Chun-Yue CY Hu Xin-Yi XY Wang Ya-Jun YJ

3 Biotech 20200222 3

Even though cell-cell adhesion molecule carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is extensively studied since the discovery, the role of CEACAM1 in different cancers is not completely clarified. In the present study, we examined CEACAM1 expression and its association with patient survival in various cancers by analysis of multiple databases. Oncomine database analysis revealed that CEACAM1 expression was upregulated in lung and pancreatic cancers, but downregulated in ...[more]

PMID: 32154045

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Project description:Patients with nonalcoholic fatty liver disease/steatohepatitis (NAFLD/NASH) commonly develop atherosclerosis through a mechanism that is not well delineated. These diseases are associated with steatosis, inflammation, oxidative stress, and fibrosis. The role of insulin resistance in their pathogenesis remains controversial. Albumin (Alb)Cre+ Cc1flox ( fl ) /fl mice with the liver-specific null deletion of the carcinoembryonic antigen-related cell adhesion molecule 1 (Ceacam1; alias Cc1) gene display hyperinsulinemia resulting from impaired insulin clearance followed by hepatic insulin resistance, elevated de novo lipogenesis, and ultimately visceral obesity and systemic insulin resistance. We therefore tested whether this mutation causes NAFLD/NASH and atherosclerosis. To this end, mice were propagated on a low-density lipoprotein receptor (Ldlr) -/- background and at 4 months of age were fed a high-cholesterol diet for 2 months. We then assessed the biochemical and histopathologic changes in liver and aortae. Ldlr-/-AlbCre+Cc1fl/fl mice developed chronic hyperinsulinemia with proatherogenic hypercholesterolemia, a robust proinflammatory state associated with visceral obesity, elevated oxidative stress (reduced NO production), and an increase in plasma and tissue endothelin-1 levels. In parallel, they developed NASH (steatohepatitis, apoptosis, and fibrosis) and atherosclerotic plaque lesions. Mechanistically, hyperinsulinemia caused down-regulation of the insulin receptor followed by inactivation of the insulin receptor substrate 1-protein kinase B-endothelial NO synthase pathway in aortae, lowering the NO level. This also limited CEACAM1 phosphorylation and its sequestration of Shc-transforming protein (Shc), activating the Shc-mitogen-activated protein kinase-nuclear factor kappa B pathway and stimulating endothelin-1 production. Thus, in the presence of proatherogenic dyslipidemia, hyperinsulinemia and hepatic insulin resistance driven by liver-specific deletion of Ceacam1 caused metabolic and vascular alterations reminiscent of NASH and atherosclerosis. Conclusion: Altered CEACAM1-dependent hepatic insulin clearance pathways constitute a molecular link between NASH and atherosclerosis.

Project description:BACKGROUND: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a multifunctional Ig-like cell adhesion molecule that has a wide range of biological functions. According to previous reports, serum CEACAM1 is dysregulated in different malignant tumours and associated with tumour progression. However, the serum CEACAM1 expression in non-small-cell lung carcinomas (NSCLC) is unclear. The different expression ratio of CEACAM1-S and CEACAM1-L isoform has seldom been investigated in NSCLC. This research is intended to study the serum CEACAM1 and the ratio of CEACAM1-S/L isoforms in NSCLC. METHODS: The expression of the serum CEACAM1 was determined by enzyme-linked immunosorbent assay. The protein expression and the location of CEACAM1 in tumours were observed by immunohistochemical staining. The CEACAM1 mRNA levels in tumour and normal adjacent tissues were measured using quantitative real-time PCR, and the expression patterns and the rate of CEACAM1-S and CEACAM1-L were analysed by reverse transcription-PCR. RESULTS: Serum CEACAM1 levels were significantly higher in NSCLC patients compared with that from normal healthy controls (P <0.0001). 17 patients (81%) among 21 showed high expression of CEACAM1 by immunohistochemical staining. Although no significant differences were found between tumour and normal tissues on mRNA expression levels of CEACAM1 (P >0.05), the CEACAM1-S and the CEACAM1-S/L (S: L) ratios were significantly higher in tumour than normal tissues (P <0.05). CONCLUSIONS: Our data indicated that the serum levels of CEACAM1 could discriminate lung cancer patients from health donors and that CEACAM1 might be a useful marker in early diagnosis of NSCLC. Moreover, our results showed that the expression patterns of CEACAM1 isoforms could be changed during oncogenesis, even when total CEACAM1 in tumour tissues did not show significant changes. Our study suggested that the expression ratios of CEACAM1-S/CEACAM1-L might be a better diagnostic indicator in NSCLC than the quantitative changes of CEACAM1.

Dataset Information

Integrated analysis of gene expression, alteration and clinical significance of carcinoembryonic antigen-related cell adhesion molecule 1 in cancer.

Publications

Integrated analysis of gene expression, alteration and clinical significance of carcinoembryonic antigen-related cell adhesion molecule 1 in cancer.

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