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      A risk score model for the prediction of osteosarcoma metastasis

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          Abstract

          Osteosarcoma is the most common primary solid malignancy of the bone, and its high mortality usually correlates with early metastasis. In this study, we developed a risk score model to help predict metastasis at the time of diagnosis. We downloaded and mined four expression profile datasets associated with osteosarcoma metastasis from the Gene Expression Omnibus. After data normalization, we performed LASSO logistic regression analysis together with 10‐fold cross validation using the GSE21257 dataset. A combination of eight genes ( RAB1 , CLEC3B , FCGBP , RNASE3 , MDL1 , ALOX5 AP , VMO1 and ALPK3 ) were identified as being associated with osteosarcoma metastasis. These genes were put into a gene risk score model, and the prediction efficiency of the model was then validated using three independent datasets ( GSE33383, GSE66673, and GSE49003) by plotting receiver operating characteristic curves. The expression levels of the eight genes in all datasets were shown as heatmaps, and gene ontology gene annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed. These eight genes play a role in cancer‐related biological processes, such as apoptosis and biosynthetic processes. Our results may aid in elucidating the possible mechanisms of osteosarcoma metastasis, and may help to facilitate the individual management of patients with osteosarcoma after treatment.

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          Most cited references26

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          Missing value estimation methods for DNA microarrays.

          Gene expression microarray experiments can generate data sets with multiple missing expression values. Unfortunately, many algorithms for gene expression analysis require a complete matrix of gene array values as input. For example, methods such as hierarchical clustering and K-means clustering are not robust to missing data, and may lose effectiveness even with a few missing values. Methods for imputing missing data are needed, therefore, to minimize the effect of incomplete data sets on analyses, and to increase the range of data sets to which these algorithms can be applied. In this report, we investigate automated methods for estimating missing data. We present a comparative study of several methods for the estimation of missing values in gene microarray data. We implemented and evaluated three methods: a Singular Value Decomposition (SVD) based method (SVDimpute), weighted K-nearest neighbors (KNNimpute), and row average. We evaluated the methods using a variety of parameter settings and over different real data sets, and assessed the robustness of the imputation methods to the amount of missing data over the range of 1--20% missing values. We show that KNNimpute appears to provide a more robust and sensitive method for missing value estimation than SVDimpute, and both SVDimpute and KNNimpute surpass the commonly used row average method (as well as filling missing values with zeros). We report results of the comparative experiments and provide recommendations and tools for accurate estimation of missing microarray data under a variety of conditions.
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            KAI1, a metastasis suppressor gene for prostate cancer on human chromosome 11p11.2.

            A gene from human chromosome 11p11.2 was isolated and was shown to suppress metastasis when introduced into rat AT6.1 prostate cancer cells. Expression of this gene, designated KAI1, was reduced in human cell lines derived from metastatic prostate tumors. KAI1 specifies a protein of 267 amino acids, with four hydrophobic and presumably transmembrane domains and one large extracellular hydrophilic domain with three potential N-glycosylation sites. KAI1 is evolutionarily conserved, is expressed in many human tissues, and encodes a member of a structurally distinct family of leukocyte surface glycoproteins. Decreased expression of this gene may be involved in the malignant progression of prostate and other cancers.
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              Osteogenic sarcoma with clinically detectable metastasis at initial presentation.

              Chemotherapy and surgery have improved the length of survival for patients with osteogenic sarcoma (OS) who present without metastatic disease. We reviewed our experience with patients with OS who presented with clinically detectable metastasis to determine the prognostic factors and the effects of surgery on the primary tumor and on metastatic disease. From 1975 to 1984 we treated 62 patients who had previously untreated OS with metastasis detected at presentation. All of these patients received intensive chemotherapy that included high-dose methotrexate; doxorubicin; and bleomycin, cyclophosphamide, and dactinomycin (BCD). Selected patients also received cisplatin. The intent of surgery was resection of the primary tumor and metastatic disease. Survival was extremely poor; only 11% of patients survived, with a median survival of 20 months. Survival was not affected by use of preoperative chemotherapy versus immediate surgery, and did not correlate with serum lactate dehydrogenase (LDH) level, alkaline phosphatase level, or the site of the primary tumor. Survival did correlate with age, location of metastatic disease, histologic response to preoperative chemotherapy, and completeness of surgical resection of all sites of tumor. Resection of all sites of tumor identified at initial presentation was necessary for survival. OS that presents with metastatic disease has a very poor prognosis with therapy, although therapy has achieved good results for patients without metastasis detected at diagnosis. Aggressive surgical resection of tumor is necessary for survival. The use of novel therapies at initial presentation is justified with this group of patients.
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                Author and article information

                Contributors
                ayabluewin@163.com
                Journal
                FEBS Open Bio
                FEBS Open Bio
                10.1002/(ISSN)2211-5463
                FEB4
                FEBS Open Bio
                John Wiley and Sons Inc. (Hoboken )
                2211-5463
                02 February 2019
                March 2019
                : 9
                : 3 ( doiID: 10.1002/feb4.2019.9.issue-3 )
                : 519-526
                Affiliations
                [ 1 ] Surgeon of Orthopedics Department II First Hospital of Qin Huangdao China
                [ 2 ] Baotou Medical College China
                [ 3 ] Department of Oncology First Hospital of Qinhuangdao China
                Author notes
                [*] [* ] Correspondence

                L. Dong, Department of Oncology, The First Hospital of Qinhuangdao, Wenhua Road No. 258, Haigang District, Qinhuangdao, Hebei, China

                Tel: +86 13333282619

                E‐mail: ayabluewin@ 123456163.com

                Article
                FEB412592
                10.1002/2211-5463.12592
                6396159
                30868060
                2c91e28c-44b1-433d-8b34-3af1f6ff2e3c
                © 2019 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 29 September 2018
                : 06 January 2019
                : 08 January 2019
                Page count
                Figures: 4, Tables: 0, Pages: 8, Words: 3755
                Funding
                Funded by: Science and Technology Program of Hebei Province
                Award ID: 162777146
                Categories
                Research Article
                Research Articles
                Custom metadata
                2.0
                feb412592
                March 2019
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.6.1 mode:remove_FC converted:01.03.2019

                metastasis: bioinformatic analysis,osteosarcoma,risk score model

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