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      The expression and prognostic significance of Drp1 in lung cancer : A bioinformatics analysis and immunohistochemistry

      , PhD a , , MD b , , MD b , , MD b , , MD b ,

      Medicine

      Wolters Kluwer Health

      Drp1, lung cancer, prognosis

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          Abstract

          Background:

          Dynamin-related protein 1 (Drp1) plays important roles in tumorigenesis, including lung cancer. However, the effect of Drp1 in lung cancer remains unclear. The present study was aimed to investigate the clinical significance and effect of Drp1 on prognosis of lung cancer.

          Methods:

          Oncomine and The Cancer Genome Atlas (TCGA) databases were selected to predict the differential expression levels of Drp1 in lung cancer. Then, 70 cases of lung cancer and normal tissues were collected and immunohistochemistry was used to detect the expression of Drp1. In addition, Kaplan–Meier Plotter database and TCGA database were used to verify the correlation between Drp1 expression and the clinical prognosis in lung cancer patients.

          Results:

          Drp1 was significantly overexpressed in lung cancer tissues based on Oncomine and TCGA databases ( P < .05). Moreover, results from immunohistochemistry showed that Drp1 protein level in lung cancer was also significantly higher than that in the matched normal tissues ( P < .05). Prognostic analysis from Kaplan–Meier Plotter database with the chosen probe IDs of 203105_s_at suggested that Drp1 was negatively correlated to overall survival (OS) of lung cancer patients (HR = 1.16, 95% CI: 1.02–1.31; P = .025), but not in the probe IDs of 226154_at (HR = 0.86, 95% CI: 0.73–1.01; P = .069). However, prognosis from TCGA database showed inconsistent results in which high expression of Drp1 was correlated with worse survival probability of all, male, female in lung adenocarcinoma ( P < .05), but not in LUSC ( P > .05).

          Conclusion:

          Drp1 was highly expressed in lung cancer based on bioinformatics analysis and tissue microarray, but there was a lot of inconsistency in prognosis depending on different levels of Drp1 from the bioinformatics analysis.

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          Most cited references 19

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          Non-small cell lung cancer.

          Most patients with non-small cell lung cancer (NSCLC) are diagnosed with advanced cancer. These guidelines only include information about stage IV NSCLC. Patients with widespread metastatic disease (stage IV) are candidates for systemic therapy, clinical trials, and/or palliative treatment. The goal is to identify patients with metastatic disease before initiating aggressive treatment, thus sparing these patients from unnecessary futile treatment. If metastatic disease is discovered during surgery, then extensive surgery is often aborted. Decisions about treatment should be based on multidisciplinary discussion.
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            Meta-Analysis of the Luminal and Basal Subtypes of Bladder Cancer and the Identification of Signature Immunohistochemical Markers for Clinical Use

            Background It has been suggested that bladder cancer can be divided into two molecular subtypes referred to as luminal and basal with distinct clinical behaviors and sensitivities to chemotherapy. We aimed to validate these subtypes in several clinical cohorts and identify signature immunohistochemical markers that would permit simple and cost-effective classification of the disease in primary care centers. Methods We analyzed genomic expression profiles of bladder cancer in three cohorts of fresh frozen tumor samples: MD Anderson (n = 132), Lund (n = 308), and The Cancer Genome Atlas (TCGA) (n = 408) to validate the expression signatures of luminal and basal subtypes and relate them to clinical follow-up data. We also used an MD Anderson cohort of archival bladder tumor samples (n = 89) and a parallel tissue microarray to identify immunohistochemical markers that permitted the molecular classification of bladder cancer. Findings Bladder cancers could be assigned to two candidate intrinsic molecular subtypes referred to here as luminal and basal in all of the datasets analyzed. Luminal tumors were characterized by the expression signature similar to the intermediate/superficial layers of normal urothelium. They showed the upregulation of PPARγ target genes and the enrichment for FGFR3, ELF3, CDKN1A, and TSC1 mutations. In addition, luminal tumors were characterized by the overexpression of E-Cadherin, HER2/3, Rab-25, and Src. Basal tumors showed the expression signature similar to the basal layer of normal urothelium. They showed the upregulation of p63 target genes, the enrichment for TP53 and RB1 mutations, and overexpression of CD49, Cyclin B1, and EGFR. Survival analyses showed that the muscle-invasive basal bladder cancers were more aggressive when compared to luminal cancers. The immunohistochemical expressions of only two markers, luminal (GATA3) and basal (KRT5/6), were sufficient to identify the molecular subtypes of bladder cancer with over 90% accuracy. Interpretation The molecular subtypes of bladder cancer have distinct clinical behaviors and sensitivities to chemotherapy, and a simple two-marker immunohistochemical classifier can be used for prognostic and therapeutic stratification. Funding U.S. National Cancer Institute and National Institute of Health.
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              Drp1-Dependent Mitochondrial Fission Plays Critical Roles in Physiological and Pathological Progresses in Mammals

              Current research has demonstrated that mitochondrial morphology, distribution, and function are maintained by the balanced regulation of mitochondrial fission and fusion, and perturbation of the homeostasis between these processes has been related to cell or organ dysfunction and abnormal mitochondrial redistribution. Abnormal mitochondrial fusion induces the fragmentation of mitochondria from a tubular morphology into pieces; in contrast, perturbed mitochondrial fission results in the fusion of adjacent mitochondria. A member of the dynamin family of large GTPases, dynamin-related protein 1 (Drp1), effectively influences cell survival and apoptosis by mediating the mitochondrial fission process in mammals. Drp1-dependent mitochondrial fission is an intricate process regulating both cellular and organ dynamics, including development, apoptosis, acute organ injury, and various diseases. Only after clarification of the regulative mechanisms of this critical protein in vivo and in vitro will it set a milestone for preventing mitochondrial fission related pathological processes and refractory diseases.
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                Author and article information

                Journal
                Medicine (Baltimore)
                Medicine (Baltimore)
                MEDI
                Medicine
                Wolters Kluwer Health
                0025-7974
                1536-5964
                November 2019
                27 November 2019
                : 98
                : 48
                Affiliations
                [a ]Department of Rehabilitation Medicine, the Second Affiliated Hospital of Nanchang University
                [b ]Department of Pulmonary and Critical Care Medicine, Jiangxi Provincial People's Hospital, Nanchang of Jiangxi, China.
                Author notes
                []Correspondence: Shengsong Chen, Department of Pulmonary and Critical Care Medicine, Jiangxi Provincial People's Hospital, Nanchang of Jiangxi, 330006, China (e-mail: chenss93@ 123456163.com ).
                Article
                MD-D-19-06320 18228
                10.1097/MD.0000000000018228
                6890372
                31770286
                Copyright © 2019 the Author(s). Published by Wolters Kluwer Health, Inc.

                This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc/4.0

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                drp1, lung cancer, prognosis

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