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      Distinct Prognostic Values of Alcohol Dehydrogenase Family Members for Non-Small Cell Lung Cancer

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          Abstract

          Background

          Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related death worldwide. The relationships of alcohol dehydrogenase (ADH) enzymes, encoded by the genes ADH1 ( 1A), ADH1B ( ADH2), ADH1C ( ADH3), ADH4, ADH5, ADH6, and ADH7, with NSCLC have not been studied. The aim of this study was to explore the associations between NSCLC prognosis and the expression patterns of ADH family members.

          Material/Methods

          The online resource Metabolic gEne RApid Visualizer was used to assess the expression patterns of ADH family members in normal and primary lung tumor tissues. The GeneMANIA plugin of Cytoscape software and STRING website were used to evaluate the relationships of the 7 ADH family members at the gene and protein levels. Gene ontology enrichment analysis and KEGG pathway analysis were performed using DAVID. The online website Kaplan-Meier Plotter was used to construct survival curves between NSCLC and ADH isoforms.

          Results

          The prognosis of patients with high expression levels of the ADH1B, ADH1C, ADH4, and ADH5 genes was better than those with low expression in adenocarcinoma and all (containing adenocarcinoma and squamous cell cancer) histological types (all P<0.05). Low expression of ADH7 was associated with a better prognosis in patients with both the adenocarcinoma and squamous cell cancer histological types ( P=9e-05). Moreover, expression of ADH family members was associated with smoking status, clinical stage, and chemotherapy status.

          Conclusions

          ADH1B, ADH1C, ADH4, ADH5, and ADH7 appear to be useful biomarkers for the prognosis of NSCLC patients.

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          Most cited references44

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          Scientific Advances in Lung Cancer 2015.

          Lung cancer continues to be a major global health problem; the disease is diagnosed in more than 1.6 million new patients each year. However, significant progress is underway in both the prevention and treatment of lung cancer. Lung cancer therapy has now emerged as a "role model" for precision cancer medicine, with several important therapeutic breakthroughs occurring during 2015. These advances have occurred primarily in the immunotherapy field and in treatments directed against tumors harboring specific oncogenic drivers. Our knowledge about molecular mechanisms for oncogene-driven tumors and about resistance to targeted therapies has increased quickly over the past year. As a result, several regulatory approvals of new agents that significantly improve survival and quality of life for patients with lung cancer who have advanced disease have occurred. The International Association for the Study of Lung Cancer has gathered experts in different areas of lung cancer research and management to summarize the most significant scientific advancements related to prevention and therapy of lung cancer during the past year.
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            MERAV: a tool for comparing gene expression across human tissues and cell types

            The oncogenic transformation of normal cells into malignant, rapidly proliferating cells requires major alterations in cell physiology. For example, the transformed cells remodel their metabolic processes to supply the additional demand for cellular building blocks. We have recently demonstrated essential metabolic processes in tumor progression through the development of a methodological analysis of gene expression. Here, we present the Metabolic gEne RApid Visualizer (MERAV, http://merav.wi.mit.edu), a web-based tool that can query a database comprising ∼4300 microarrays, representing human gene expression in normal tissues, cancer cell lines and primary tumors. MERAV has been designed as a powerful tool for whole genome analysis which offers multiple advantages: one can search many genes in parallel; compare gene expression among different tissue types as well as between normal and cancer cells; download raw data; and generate heatmaps; and finally, use its internal statistical tool. Most importantly, MERAV has been designed as a unique tool for analyzing metabolic processes as it includes matrixes specifically focused on metabolic genes and is linked to the Kyoto Encyclopedia of Genes and Genomes pathway search.
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              The antiproliferative effect of C2-ceramide on lung cancer cells through apoptosis by inhibiting Akt and NFκB

              The anticancer effects of ceramide have been reported in many types of cancers but less in lung cancer. In this study, we used C2-ceramide to further investigate its possible anticancer effects and mechanisms on non-small cell lung cancer (NSCLC) H1299 cells. The result of cell proliferation in terms of trypan blue assay showed high dose of C2-ceramide inhibited cell survival after 24 h treatment. The flow cytometry-based assays indicated the effect of apoptosis, chromatin condensation, and G1 arrest in terms of Annexin V/propidium iodide (PI), DAPI, and PI stainings, respectively. Moreover, the decreased protein level of p-Akt, p-NFκB, survivin and cyclin A2 were detected by Western blot assay. Taken together, these results indicated the antiproliferative effect of C2-ceramide is majorly responsible for cell apoptosis in lung cancer H1299 cells.
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                Author and article information

                Journal
                Med Sci Monit
                Med. Sci. Monit
                Medical Science Monitor
                Medical Science Monitor : International Medical Journal of Experimental and Clinical Research
                International Scientific Literature, Inc.
                1234-1010
                1643-3750
                2018
                29 May 2018
                : 24
                : 3578-3590
                Affiliations
                [1 ]Department of Health Management and Division of Physical Examination, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, P.R. China
                [2 ]Department of Respiratory Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, P.R. China
                Author notes
                Corresponding Author: Jianquan Zhang, e-mail: jqzhang2002@ 123456126.com
                [A]

                Study Design

                [B]

                Data Collection

                [C]

                Statistical Analysis

                [D]

                Data Interpretation

                [E]

                Manuscript Preparation

                [F]

                Literature Search

                [G]

                Funds Collection

                Article
                910026
                10.12659/MSM.910026
                6003262
                29808834
                e9ff6c27-de4f-4d12-abd6-5325ddd4d137
                © Med Sci Monit, 2018

                This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International ( CC BY-NC-ND 4.0)

                History
                : 18 March 2018
                : 02 May 2018
                Categories
                Lab/In Vitro Research

                alcohol dehydrogenase,biological markers,carcinoma, non-small-cell lung,multigene family,prognosis

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