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      Expression Differentiation Is Not Helpful in Identifying Prognostic Genes Based on TCGA Datasets

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          Abstract

          A routine pipeline seems very common in many cancer studies that expression differentiation might be helpful in identifying prognostic molecules. There also exists a striking unanimity that molecules upregulated in cancer usually shorten survival, while downregulated ones have the opposite effect. In this study, based on the transcriptional profiles of 18 malignancies, cancer and corresponding adjacent normal tissues were used to calculate differential scores. Cox correlation coefficients of global genes were also calculated to denote survival association. The relationship between expression differentiation and survival association has been extensively studied in 18 malignancy types. Contradictory to our stereotypic research pattern, expression differentiation between cancer and adjacent normal tissues was proven irrelevant to corresponding survival correlation. Surprisingly, the more stringent cutoff we used in differentially expressed gene identification, the less prognostic information we would obtain from the collected gene groups. Moreover, the direction of dysregulated genes in cancer was irrelevant to the direction of corresponding survival correlation. Cancer-normal expression differentiation is irrelevant to genes’ survival correlation in multiple cancers and, therefore, not helpful in identifying prognostic genes. For future studies, it is more sensible to look into another alternative rather than collect differentially expressed molecules in the initial step.

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          Dabrafenib plus trametinib in patients with BRAFV600-mutant melanoma brain metastases (COMBI-MB): a multicentre, multicohort, open-label, phase 2 trial.

          Dabrafenib plus trametinib improves clinical outcomes in BRAFV600-mutant metastatic melanoma without brain metastases; however, the activity of dabrafenib plus trametinib has not been studied in active melanoma brain metastases. Here, we report results from the phase 2 COMBI-MB trial. Our aim was to build on the current body of evidence of targeted therapy in melanoma brain metastases through an evaluation of dabrafenib plus trametinib in patients with BRAFV600-mutant melanoma brain metastases.
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            Lin28b is sufficient to drive liver cancer and necessary for its maintenance in murine models.

            Lin28a/b are RNA-binding proteins that influence stem cell maintenance, metabolism, and oncogenesis. Poorly differentiated, aggressive cancers often overexpress Lin28, but its role in tumor initiation or maintenance has not been definitively addressed. We report that LIN28B overexpression is sufficient to initiate hepatoblastoma and hepatocellular carcinoma in murine models. We also detected Lin28b overexpression in MYC-driven hepatoblastomas, and liver-specific deletion of Lin28a/b reduced tumor burden, extended latency, and prolonged survival. Both intravenous siRNA against Lin28b and conditional Lin28b deletion reduced tumor burden and prolonged survival. Igf2bp proteins are upregulated, and Igf2bp3 is required in the context of LIN28B overexpression to promote growth. Therefore, multiple murine models demonstrate that Lin28b is both sufficient to initiate liver cancer and necessary for its maintenance.
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              CD73 Expression Is an Independent Prognostic Factor in Prostate Cancer.

              CD73 is an adenosine-generating ecto-enzyme that suppresses antitumor immunity in mouse models of cancer, including prostate cancer. Although high levels of CD73 are associated with poor prognosis in various types of cancer, the clinical impact of CD73 in prostate cancer remains unclear.
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                Author and article information

                Contributors
                Journal
                Mol Ther Nucleic Acids
                Mol Ther Nucleic Acids
                Molecular Therapy. Nucleic Acids
                American Society of Gene & Cell Therapy
                2162-2531
                06 March 2018
                01 June 2018
                06 March 2018
                : 11
                : 292-299
                Affiliations
                [1 ]Department of Oncology, The Affiliated Hospital of Qingdao University, Qingdao 266003, Shandong Province, China
                Author notes
                []Corresponding author: Xue Yang, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Shinan District, Qingdao 266003, China. yxue0409@ 123456outlook.com
                [∗∗ ]Corresponding author: Zhuang Yu, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Shinan District, Qingdao 266003, China. yuzhuang2002@ 123456163.com
                Article
                S2162-2531(18)30029-5
                10.1016/j.omtn.2018.02.013
                5992444
                29858064
                10c0af5f-1d56-44db-b491-d7356f644c70
                © 2018 The Authors

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 27 November 2017
                : 28 February 2018
                Categories
                Article

                Molecular medicine
                expression differentiation,prognostic genes,pan-cancer analysis
                Molecular medicine
                expression differentiation, prognostic genes, pan-cancer analysis

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