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      Clinicopathological Characteristics and Prognosis of Signet Ring Gastric Cancer: A Population-Based Study


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          To better define the clinicopathologic characteristics of signet ring cell (SRC) gastric cancer and build a prognostic model for it.


          SRC patient information from 2010 to 2015 were identified using Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier method and log-rank test were used to estimate Overall survival (OS) and to determine associations with histologic subtypes. In COX proportional hazards regression model–based univariate and multivariate analyses, significant variables for construction of a nomogram were screened out. The nomogram was validated by means of the concordance index (CI), calibration plots, and receiver operating characteristics (ROCs) curves.


          A total of 11,363 gastric cancer patients were enrolled. On dividing the patients into SRC, well-to-moderately differentiated (WMD) adenocarcinoma, and poorly differentiated (PD) adenocarcinoma, differences among these subgroups emerged. SRC patients were more likely to occur in female and young patients than other histologic subtypes. Larger tumors, stage T4, and node stage N3 were more likely to be found in the SRC group. The survival for SRC patients was better than non-SRC patients in stage I. Univariate and multivariate analyses identified age, tumor site, larger tumor size, advanced T classification, advanced N classification, advanced TNM stage, and surgery of primary site as independent prognostic indicators. Then an OS nomogram was formulated.


          SRC had distinct clinicopathological characteristics. The nomogram provided an accurate tool to evaluate the prognosis of SRC.

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          Most cited references24

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          Estimates of the worldwide incidence and mortality from 27 major cancers and for all cancers combined for 2012 are now available in the GLOBOCAN series of the International Agency for Research on Cancer. We review the sources and methods used in compiling the national cancer incidence and mortality estimates, and briefly describe the key results by cancer site and in 20 large "areas" of the world. Overall, there were 14.1 million new cases and 8.2 million deaths in 2012. The most commonly diagnosed cancers were lung (1.82 million), breast (1.67 million), and colorectal (1.36 million); the most common causes of cancer death were lung cancer (1.6 million deaths), liver cancer (745,000 deaths), and stomach cancer (723,000 deaths). © 2014 UICC.
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            Development and validation of a prognostic nomogram for recurrence-free survival after complete surgical resection of localised primary gastrointestinal stromal tumour: a retrospective analysis.

            Adjuvant imatinib mesylate prolongs recurrence-free survival (RFS) after resection of localised primary gastrointestinal stromal tumours (GIST). We aimed to develop a nomogram to predict RFS after surgery in the absence of adjuvant therapy to help guide patient selection for adjuvant imatinib therapy. A nomogram to predict RFS based on tumour size (cm), location (stomach, small intestine, colon/rectum, or other), and mitotic index ( or =5 mitoses per 50 high-power fields) was developed from 127 patients treated at Memorial Sloan-Kettering Cancer Center (MSKCC), New York, NY, USA. The nomogram was tested in patients from the Spanish Group for Research on Sarcomas (GEIS; n=212) and the Mayo Clinic, Rochester, MN, USA (Mayo; n=148). The nomogram was assessed by calculating concordance probabilities and testing calibration of predicted RFS with observed RFS. Concordance probabilities were also compared with those of three commonly used staging systems. The nomogram had a concordance probability of 0.78 (SE 0.02) in the MSKCC dataset, and 0.76 (0.03) and 0.80 (0.02) in the validation cohorts. Nomogram predictions were well calibrated. Inclusion of tyrosine kinase mutation status in the nomogram did not improve its discriminatory ability. Concordance probabilities of the nomogram were better than those of the two NIH staging systems (0.76 [0.03] vs 0.70 [0.04, p=0.04] and 0.66 [0.04, p=0.01] in the GEIS validation cohort; 0.80 [0.02] vs 0.74 [0.02, p=0.04] and 0.78 [0.02, p=0.05] in the Mayo cohort) and similar to those of the AFIP-Miettinen staging system (0.76 [0.03] vs 0.73 [0.004, p=0.28] in the GEIS cohort; 0.80 [0.02] vs 0.76 [0.003, p=0.09] in the Mayo cohort). Nomogram predictions of RFS seemed better calibrated than predictions made with the AFIP-Miettinen system. The nomogram accurately predicts RFS after resection of localised primary GIST and could be used to select patients for adjuvant imatinib therapy.
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              Gastric cancer: somatic genetics as a guide to therapy.

              Gastric cancer is the leading cause of cancer-related mortality across the world, with poor prognosis and a median overall survival of ≤12 months for advanced stage gastric cancer. Environmental, genetic and other predisposing factors contribute to the development of gastric cancer and a predominant factor was found to be infection of Helicobacter pylori Advances in understanding the deranged signalling pathways that are critical for normal cellular homeostasis helped in the development of novel drugs that target specific proteins and pathways to curtail the growth of gastric cancer. Genetic studies revealed several single nucleotide polymorphisms, chromosomal aberrations and epigenetic alterations that likely play a major role in elevating the susceptibility to develop gastric cancer. Methylation pattern of specific genes may likely prove to be a valid biomarker for early detection of gastric cancer, but much progress is needed to establish specific markers. Important developments have been made in targeting human epidermal growth factor receptor-2 and vascular endothelial growth factor receptor 2 for treating advanced gastro-oesophageal junction cancer, using specific monoclonal antibodies. Lack of efficacy with regard to targeting other signalling pathways including mesenchymal-epithelial transition/hepatocyte growth factor and mammalian target of rapamycin is probably due to suboptimal patient selection for these clinical trials, which is probably due to the lack of appropriate biomarkers, to decide on responsive patient population. Besides the development of antagonists for the cell growth-related signalling pathways, advances are also being made to tackle gastric cancer by immunotherapies, targeting immune check-points, which may hold promise for better treatment options in future.

                Author and article information

                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                13 August 2021
                : 11
                : 580545
                [1] 1Department of Abdominal Medical Oncology, Institute of Cancer and Basic Medicine (ICBM), Chinese Academy of Sciences, Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital , Hangzhou, China
                [2] 2The Second Clinical Medical College of Zhejiang Chinese Medical University , Hangzhou, China
                [3] 3Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital and Institute , Beijing, China
                [4] 4Department of Cell Biology, Zhejiang University School of Medicine , Hangzhou, China
                [5] 5Department of Gastric Surgery, Institute of Cancer and Basic Medicine (ICBM), Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Chinese Academy of Sciences , Hangzhou, China
                Author notes

                Edited by: Alberto Biondi, Catholic University of the Sacred Heart, Italy

                Reviewed by: Jing Gao, Chinese Academy of Medical Sciences and Peking Union Medical College, China; Prashanth Kumar M. V., JSS Academy of Higher Education and Research, India

                *Correspondence: Jieer Ying, jieerying@ 123456aliyun.com ; Zhiyuan Xu, getfar@ 123456foxmail.com

                †These authors have contributed equally to this work

                This article was submitted to Gastrointestinal Cancers, a section of the journal Frontiers in Oncology

                Copyright © 2021 Wei, Gao, Qi, Yuan, Li, Xu, Luo, Chen, Zhuo, Xu and Ying

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                : 06 July 2020
                : 16 June 2021
                Page count
                Figures: 5, Tables: 4, Equations: 0, References: 24, Pages: 9, Words: 3693
                Original Research

                Oncology & Radiotherapy
                carcinoma,signet ring cell,nomograms,stomach neoplasms,prognosis
                Oncology & Radiotherapy
                carcinoma, signet ring cell, nomograms, stomach neoplasms, prognosis


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