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      A 21-gene Support Vector Machine classifier and a 10-gene risk score system constructed for patients with gastric cancer

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          Abstract

          Gastric cancer (GC) ranks fifth in terms of incidence and third in terms of tumor mortality worldwide. The present study was designed to construct a Support Vector Machine (SVM) classifier and risk score system for GC. The GSE62254 (training set) and GSE26253 (validation set 2) datasets were downloaded from the Gene Expression Omnibus database. Furthermore, the gene expression profile of GC (validation set 1) was obtained from The Cancer Genome Atlas database. Differentially expressed genes (DEGs) between recurrent and non-recurrent samples were determined using the limma package. The feature genes were selected using the Caret package, and an SVM classifier was built using the e1071 package. Using the penalized package, the optimal predictive genes for constructing a risk score system were screened. Finally, stratification analysis of clinical factors and pathway enrichment analysis were performed using Gene Set Enrichment Analysis. A total of 239 DEGs were identified in GSE62254, among which 114 DEGs were significantly associated with both recurrence-free survival and overall survival. Subsequently, 21 feature genes were screened from the 114 DEGs, and an SVM classifier was built. A risk score system for survival prediction was constructed, following the selection of 10 optimal genes, including A-kinase anchoring protein 12, angiopoietin-like protein 1, cysteine-rich sequence 1, myeloid/lymphoid or mixed-lineage leukemia, translocated to chromosome 11, neuron navigator 3, neurobeachin, nephroblastoma overexpressed, pleiotrophin, tumor suppressor candidate 3 and zinc finger and SCAN domain containing 18. The stratification analysis revealed that pathological stage was an independent prognostic clinical factor in the high-risk group. Additionally, eight significant pathways were associated with the 10-gene signature. The SVM classifier and risk score system may be applied for classifying and predicting the prognosis of patients with GC, respectively.

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          Regulation of the actin cytoskeleton in cancer cell migration and invasion.

          Malignant cancer cells utilize their intrinsic migratory ability to invade adjacent tissues and the vasculature, and ultimately to metastasize. Cell migration is the sum of multi-step processes initiated by the formation of membrane protrusions in response to migratory and chemotactic stimuli. The driving force for membrane protrusion is localized polymerization of submembrane actin filaments. Recently, several studies revealed that molecules that link migratory signals to the actin cytoskeleton are upregulated in invasive and metastatic cancer cells. In this review, we summarize recent progress on molecular mechanisms of formation of invasive protrusions used by tumor cells, such as lamellipodia and invadopodia, with regard to the functions of key regulatory proteins of the actin cytoskeleton; WASP family proteins, Arp2/3 complex, LIM-kinase, cofilin, and cortactin.
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            Recurrence following curative resection for gastric carcinoma.

            The diagnosis and treatment of recurrent gastric cancer remains difficult. The aim of this study was to determine the risk factors for recurrence of gastric cancer and the prognosis for these patients. Of 2328 patients who underwent curative resection for gastric cancer from 1987 to 1995, 508 whose recurrence was confirmed by clinical examination or reoperation were studied retrospectively. The risk factors that determined the recurrence patterns and timing were investigated by univariate and multivariate analysis. The mean time to recurrence was 21.8 months and peritoneal recurrence was the most frequent (45.9 per cent). Logistic regression analysis showed that serosal invasion and lymph node metastasis were risk factors for all recurrence patterns and early recurrence (at 24 months or less). In addition, independent risk factors involved in each recurrence pattern included younger age, infiltrative or diffuse type, undifferentiated tumour and total gastrectomy for peritoneal recurrence; older age and larger tumour size for disseminated, haematogenous recurrence; and older age, larger tumour size, infiltrative or diffuse type, proximally located tumour and subtotal gastrectomy for locoregional recurrence. Other risk factors for early recurrence were infiltrative or diffuse type and total gastrectomy. Reoperation for cure was possible in only 19 patients and the mean survival time after conservative treatment or palliative operation was less than 12 months. The risk factors for each recurrence pattern and timing of gastric cancer can be predicted by the clinicopathological features of the primary tumour. Since the results of treatment remain dismal, studies of perioperative adjuvant therapy in an attempt to reduce recurrence are warranted.
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              Gastric cancer: epidemiology and risk factors.

              Gastric cancer is one of the major malignancies in the world. This article summarizes the current understanding of the worldwide burden of this disease, its geographic variation, and temporal trends. An overview is presented of known risk factors, including genetic, dietary, and behavioral, but focuses on Helicobacter pylori infection as the most important factor in noncardia gastric cancer. When the data and the literature allow, we distinguish between cardia and noncardia sub-sites, as it is now clear that these two anatomic locations present distinct and sometimes opposite epidemiological characteristics. Copyright © 2013 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Mol Med Rep
                Mol Med Rep
                Molecular Medicine Reports
                D.A. Spandidos
                1791-2997
                1791-3004
                January 2020
                21 November 2019
                21 November 2019
                : 21
                : 1
                : 347-359
                Affiliations
                Department of Gastrointestinal Surgery, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 214062, P.R. China
                Author notes
                Correspondence to: Dr Bojian Fei, Department of Gastrointestinal Surgery, Affiliated Hospital of Jiangnan University, 200 Huihe Road, Wuxi, Jiangsu 214062, P.R. China, E-mail: jxjianghuijx@ 123456163.com
                Article
                mmr-21-01-0347
                10.3892/mmr.2019.10841
                6896370
                31939629
                3b11e4eb-8815-4dd5-9ac8-0ee6e81afedc
                Copyright: © Jiang et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

                History
                : 09 March 2019
                : 25 October 2019
                Categories
                Articles

                gc,degs,svm,risk score system,stratification analysis
                gc, degs, svm, risk score system, stratification analysis

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