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      Development and validation of a survival model for thyroid carcinoma based on autophagy-associated genes

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          Abstract

          Abnormalities in autophagy-related genes (ARGs) are closely related to the occurrence and development of thyroid carcinoma (THCA). However, the effect of ARGs on the prognosis of THCA remains unclear. Here, by analyzing data from TCGA, 26 differentially expressed ARGs were screened. Cox regression and Lasso regression were utilized to analyze the prognosis of the training group, and a risk model was constructed. Our results show that low-risk patients had better overall survival (OS) than high-risk patients, and the area under the ROC curve in the training and testing groups was significant (3-year AUC, 0.735 vs 0.796; 5-year AUC, 0.821 vs 0.804). In addition, a comprehensive analysis of the 5 identified ARGs demonstrated that most of them were related to OS in THCA patients, and two of them (CX3CL1 and CDKN2A) were differentially expressed in THCA and normal thyroid tissues at the protein level. GSEA suggested that the inactivation of the cell defense system and the activation of some classical tumor signaling pathways are important driving forces for the progression of THCA. This study demonstrated that the 5 ARGs in the survival model are promising multidimensional biomarkers for the diagnosis, prognosis, and treatment of THCA.

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          Most cited references39

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          Mechanism and medical implications of mammalian autophagy

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            Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor.

            The biochemical properties of beclin 1 suggest a role in two fundamentally important cell biological pathways: autophagy and apoptosis. We show here that beclin 1-/- mutant mice die early in embryogenesis and beclin 1+/- mutant mice suffer from a high incidence of spontaneous tumors. These tumors continue to express wild-type beclin 1 mRNA and protein, establishing that beclin 1 is a haploinsufficient tumor suppressor gene. Beclin 1-/- embryonic stem cells have a severely altered autophagic response, whereas their apoptotic response to serum withdrawal or UV light is normal. These results demonstrate that beclin 1 is a critical component of mammalian autophagy and establish a role for autophagy in tumor suppression. They both provide a biological explanation for recent evidence implicating beclin 1 in human cancer and suggest that mutations in other genes operating in this pathway may contribute to tumor formation through deregulation of autophagy.
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              Emerging functions of the EGFR in cancer

              The physiological function of the epidermal growth factor receptor (EGFR) is to regulate epithelial tissue development and homeostasis. In pathological settings, mostly in lung and breast cancer and in glioblastoma, the EGFR is a driver of tumorigenesis. Inappropriate activation of the EGFR in cancer mainly results from amplification and point mutations at the genomic locus, but transcriptional upregulation or ligand overproduction due to autocrine/paracrine mechanisms has also been described. Moreover, the EGFR is increasingly recognized as a biomarker of resistance in tumors, as its amplification or secondary mutations have been found to arise under drug pressure. This evidence, in addition to the prominent function that this receptor plays in normal epithelia, has prompted intense investigations into the role of the EGFR both at physiological and at pathological level. Despite the large body of knowledge obtained over the last two decades, previously unrecognized (herein defined as ‘noncanonical’) functions of the EGFR are currently emerging. Here, we will initially review the canonical ligand‐induced EGFR signaling pathway, with particular emphasis to its regulation by endocytosis and subversion in human tumors. We will then focus on the most recent advances in uncovering noncanonical EGFR functions in stress‐induced trafficking, autophagy, and energy metabolism, with a perspective on future therapeutic applications.
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                Author and article information

                Journal
                Aging (Albany NY)
                Aging
                Aging (Albany NY)
                Impact Journals
                1945-4589
                15 October 2020
                14 October 2020
                : 12
                : 19
                : 19129-19146
                Affiliations
                [1 ]Public Laboratory, Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin Medical University, Tianjin 30000, China
                [2 ]Department of Otorhinolaryngology, Head and Neck Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, China
                [3 ]Department of Otolaryngology-Head and Neck Surgery, Stanford University School of Medicine, Stanford, CA 94305, USA
                [4 ]Department of Internal Medicine, Stanford University School of Medicine, Stanford, USA 94305, USA
                [5 ]Department of Otorhinolaryngology, Head and Neck surgery, Wuhan Central Hospital, Wuhan 430014, China
                [6 ]Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
                Author notes
                [*]

                Equal contribution

                Correspondence to: Tao Zhou; email: entzt2013@hust.edu.cn
                Correspondence to: Haiying Sun; email: momo426@stanford.edu
                Correspondence to: Xiong Chen; email: zn_chenxiong@126.com
                Article
                103715
                10.18632/aging.103715
                7732287
                33055358
                87deb673-57db-49c2-9765-de665b44930d
                Copyright: © 2020 Han et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 21 April 2020
                : 29 June 2020
                Categories
                Research Paper

                Cell biology
                thyroid carcinoma,autophagy-related genes,tcga database,prognosis
                Cell biology
                thyroid carcinoma, autophagy-related genes, tcga database, prognosis

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