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World Journal of Meta-AnalysisWorld J Meta-Anal 2016 February 26; 4(1): 1-9

Published by Baishideng Publishing Group Inc

ISSN 2308-3840 (online)

The World Journal of Meta-Analysis Editorial Board consists of 400 members, representing a team of worldwide experts in clinical meta-analysis research. They are from 41 countries, including Argentina (2), Australia (3), Austria (1), Belgium (5), Brazil (11), Canada (16), Chile (3), China (121), Croatia (1), Egypt (1), Finland (4), France (2), Germany (9), Greece (11), Hungary (2), India (12), Iran (2), Ireland (1), Israel (2), Italy (41), Japan (5), Lithuania (1), Malaysia (1), Netherlands (8), New Zealand (1), Norway (1), Peru (1), Poland (4), Portugal (6), Romania (1), Saudi Arabia (4), Singapore (3), South Africa (1), South Korea (7), Spain (8), Sri Lanka (2), Sudan (1), Switzerland (2), Thailand (4), Turkey (3), United Kingdom (22), and United States (64).

Editorial Board2013-2018

EDITOR-IN-CHIEFGiuseppe Biondi-Zoccai, Latina

GUEST EDITORIAL BOARD MEMBERSBo-Ying Bao, TaichungHsing-Yi Chang, MaoliChing-Chi Chi, ChiayiKuo-Liong Chien, TaipeiChien-Chang Lee, DoliouHung-Chang Lee, HsinchuHenry WC Leung, TaoyuanYC Su, ChiayiJauyih Tsauo, Taipei

MEMBERS OF THE EDITORIAL BOARD

ArgentinaJ Mariani, Ciudad Autónoma de Buenos AiresMarcelo Signorini, Provincia de Santa Fe

Australia

Mark Boschen, SouthportTerry Boyle, PerthAndy Kim Ho Lim, Melbourne

Austria

Patrick Sadoghi, Graz

Belgium

Marc Arbyn, BrusselsChristophe Demoulin, LiegeSascha Colen, PellenbergP Lehert, MonsSteve Majerus, Liege

Brazil

Euclides Castilho, Sao PauloLuciana Tricai Cavalini, Rio de JaneiroRegina El Dib, BotucatuAlexandre Fachini, AraraquaraGuilherme Francisco, Sao PauloBruno Gualano, Sao PauloFC Paes-Barbosa, Campo GrandeRachel Riera, Sao PauloInajara Rotta, CuritibaMarcos Sousa, Belo HorizonteFelipe Francisco Tuon, Curitiba

Canada

Caroline Barakat-Haddad, TorontoA Baranchuk, KingstonMohammad Bashashati, CalgaryAlonso Carrasco-Labra, HamiltonEugene Crystal, TorontoEdiriweera Desapriya, VancouverA Fairchild, EdmontonAlejandro Lazo-Langner, LondonMichel Lucas, QuébecAlex Soroceanu, Halifax

Mohamed Ali Tagin, WinnipegSiamak Bashardoust Tajali, LondonSam Michael Wiseman, VancouverRebecca KS Wong, TorontoClement Zai, TorontoKonstantine K Zakzanis, Toronto

ChileAlonso Carrasco-Labra, HamiltonRomina Brignardello Petersen, SantiagoLuis A Quiñones, Santiago

China

Yi-Xi Bao, Chongqing Janita Chau, Hong KongJia-Xu Chen, BeijingShao-Jie Chen, ChongqingJin-Fei Chen, NanjingHao-Yu Chen, ShantouChing-Lung Cheung, Hong KongWen-Peng Cui, ChangchunCong Dai, ShenyangBo Deng, ChongqingQiang Du, ShenyangJian Fei, ShanghaiChun Gao, BeijingWei-Hong Ge, NanjingAi-Hua Gu, NanjingXiao-Xiang Guan, NanjingZhi-Yong Guo, GuangzhouChuan-Yong Guo, ShanghaiZhi-Wei He, DongguanBen He, Shanghai

WJMA|www.wjgnet.com I May 26, 2013

Guo-Wei He, TianjinG Huang, ShanghaiBing-Yang Ji, BeijingJing Jiang, ChangchunJoey Sum Wing Kwong, Hong KongWei-Dong Leng, ShiyanLe-Qun Li, NanningXiao-Ping Li, ChengduJian-Sheng Li, ZhengzhouJing-Cheng Li, ChongqingJun-Sheng Li, NanjingYan-Yan Li, NanjingHua Liu, NanchongTong Liu, TianjinAi-Ping Lu, Hong KongYing Luo, KunmingChao Ma, ShanghaiJie Ma, Xi'anXiang-Yu Ma, ChongqingYan-Lei Ma, ShanghaiWei Nie, ShanghaiWen-Quan Niu, ShanghaiWen-Sheng Pan, HangzhouShi-Qiang Shen, WuhanXiang-Chun Shen, GuiyangRui-Hua Shi, NanjingYong-Bing Shi, SuzhouKe-Qing Shi, WenzhouMarcelo Signorini, Hong KongZhi-Yuan Song, ChongqingQing-Min Sun, NanjingYi-Hong Sun, BeijingShi-Qiao Tan, ChengduSQ Tan, ChengduYong Tang, TianjinJiu-Lai Tang, HefeiNa-Ping Tang, ShanghaiJian-Cheng Tu, WuhanBin Wang, BeijingDao-Rong Wang, YangzhouJing Wang, ChangshuYu-Ting Wang, ChengduXi-Shan Wang, HarbinFu-Zhou Wang, NanjingBing Xia, WuhanHong-Xia Wang, ShanghaiZhen-Ning Wang, ShenyangNa Wang, ShijiazhuangShu-Kui Wang, WuhanXing-Huan Wang, WuhanWei Wang, WuxiCong-Xia Wang, Xi'anFeng Xie, ShanghaiZi-Qiang Xin, BeijingDan Xing, TianjinJun Xiong, NanchangXi-Ping Xu, GuangzhouLin Xu, NanjingZhuo-Qun Xu, WuxiHui-Ping Xue, ShanghaiTian Yang, ChangchunShuan-Ying Yang, Xi'anYi-Cong Ye, BeijingYan-Wei Yin, BeijingZi Yin, Guangzhou

Ym Yin, NanjingBin Yu, GuangzhouYun-Xian Yu, HangzhouLing Zhang, BeijingBei-Bei Zhang, ChengduLi-Li Zhang, ChongqingQiu Zhang, HefeiShuo Zhang, ShenyangYou-Cheng Zhang, LanzhouJian Zhang, ShanghaiJun-Hua Zhang, TianjinYu-Rong Zhang, Xi'anZhong-Heng Zhang, JinhuaHai-Tao Zhao, BeijingPan Zhao, BeijingYu-Lan Zhao, ShanghaiJie-Jiao Zheng, ShanghaiXue-Sheng Zheng, ShanghaiGuo-Qing Zheng, WenzhouMing-Hua Zheng, WenzhouCui-Hong Zheng, WuhanLai-Ping Zhong, ShanghaiTian-Biao Zhou, NanningPeng Zhou, ShanghaiPing Zhou, WuhanKun-Ju Zhu, ZhanjiangXiao-Ping Zou, Nanjing

Croatia

Miljenko Franic, Zagreb

Egypt

Ashraf Fawzy Nabhan, Cairo

FinlandJouni JK Jaakkola, OuluVille Kyto, TurkuJouko Miettunen, OuluR Quansah, Oulu

France

Alain Braillon, AmiensFrancesco Fiorica, Ferrara

Germany

Tonio Ball, FreiburgRobert Bergholz, HamburgJan Brunkwall, CologneHolger Cramer, EssenJoseph Kambeitz, MunichSascha Meyer, HomburgThomas Nickl-Jockschat, AachenMartin Pinquart, MarburgRobert Schier, Cologne

Greece

Vangelis G Alexiou, AthensStefanos Bonovas, AthensAthanasios Papatsoris, AthensIrini Chatziralli, AthensDimitrios Daoussis, PatrasPagona Lagiou, AthensJohn Goudakos, ThessalonikiSavas Grigoriadis, ThessalonikiKonstantinos A Toulis, ThessalonikiSotirios Tsiodras, AthensNikolaos Tsoukalas, Athens

Hungary

Balazs Gyorffy, BudapestIstvan Wittmann, Pecs

India

Ritesh Agarwal, ChandigarhGiridhara R Babu, BangaloreSubho Chakrabarti, ChandigarhY Madhavi, New DelhiTanu Midha, KanpurKameshwar Prasad, New DelhiKaushal Kishor Prasad, ChandigarhKrishna Undela, MysoreSingh Rajender, LucknowVinod Ravindran, KozhikodeV Shetty, MumbaiR Umaya Suganthi, Bangalore

Iran

Nejat Mahdieh, IlamSadeghi Ramin, Mashhad

Ireland

Ian Conrick-Martin, Dublin

Israel

Uri Kopylov, Ramat GanMeir Lotan, Kfar-Saba

Italy

Umberto Aguglia, CatanzaroAlessandro Antonelli, PisaAnnalisa Blasetti, ChietiFrancesco Brigo, MeranoEmanuele Cereda, PaviaEmanuele Cigna, RomeRoberto Cirocchi, TerniBernardo Cortese, Milano

WJMA|www.wjgnet.com II May 26, 2013

Alessandro Cucchetti, BolognaGianfranco Damiani, RomeFabrizio D'Ascenzo, TurinMassimo Del Fabbro, MilanoValeria Fadda, FlorenceAlessandro Fancellu, SassariGiuseppe Ferrante, MilanVirginia Festa, RomeFrancesco Fiorica, FerraraGuglielmo Giraldi, RomeJenny Guidi, BolognaLorenzo Loffredo, RomeAndrea Messori, FirenzeEliano Pio Navarese, BydgoszczStefano Omboni, Solbiate ArnoAlvisa Palese, UdineStefano Palomba, Reggio Emilia StefanoCarlo Perricone, RomeMario Petretta, NaplesAlessandro Pezzini, BresciaGianluca Pontone, MilanPaolo Emilio Puddu, RomeAndrea Rognoni, NovaraGiuseppe Scalabrino, MilanCittà della Salute e della Scienza, TurinFabrizio Sgolastra, L'AquilaMaria Lucia Specchia, RomeStefano Trastulli, TerniFabio Tine, PalermoNereo Vettoretto, ChiariAlberto Vianello, PerugiaLuigi Zorcolo, Cagliari

Japan

Nguyen Tien Huy, NagasakiHiroharu Kamioka, TokyoKoji Kawakami, KyotoKeitaro Matsuo, NagoyaKazushi Okamoto, Nagoya

Lithuania

Edmundas Kadusevicius, Kaunas

Malaysia

SP Pani, Ipoh

Netherlands

Michel van den Bekerom, AmsterdamDimitra Dodou, DelftD Haverkamp, AmsterdamVassilios Koussoulas, DrachtenBJ Polder, NijmegenTheo Stijnen, LeidenRNM Weijers, AmsterdamJoost de Winter, Delft

New Zealand

Shaofeng Li, Auckland

Norway

Eivind Berge, Oslo

Peru

Rafael Bolaños Díaz, Lima

Poland

Maciej Banach, LodzKrzysztof Jonderko, SosnowiecJolanta Lissowska, WarsawMaciej Plaszewski, Warsaw

Portugal

Daniel Caldeira, LisboaJ Costa, LisbonAna Miguel, CoimbraManuel Morgado, CovilhBárbara Peleteiro, PortoRui Torres, Paredes

Romania

Fratila Ovidiu, Oradea

Saudi Arabia

Hazem M Al-Mandeel, RiyadhEzzeldin M Ibrahim, JeddahMutahir A Tunio, RiyadhHayfaa A Wahabi, Riyadh

Singapore

Nikos LD Chatzisarantis, SingaporeEdwin Choon Wyn Lim, SingaporeRoger Ho, Singapore

South Africa

Alaine Umubyeyi Nyaruhirira, Pretoria

South Korea

Jung-Hee Kim, Cheonan

Hyangsook Lee, SeoulMyeong Soo Lee, DaejeonChi-Un Pae, BucheonYong Hyun Park, Yangsan Jae Hong Seo, SeoulYong Sang Song, Seoul

Spain

Pablo Avanzas, OviedoJoan Cid, BarcelonaJoaquin de Haro, MadridJoan Guardia-Olmos, BarcelonaNabil Halaihlel, ZaragozaJA Monge-Argilés, AlicanteRaul Moreno, MadridInés Velasco, Aracena

Sri LankaRanil Jayawardena, ColomboPriyanga Ranasinghe, Colombo

SwitzerlandJay P Singh, ZurichGiorgio Treglia, Bellinzona

Sudan

Samir MH Shaheen, Khartoum

Thailand

Chuenjid Kongkaew, PhitsanulokManop Pithukpakorn, BangkokPiyamitr Sritara, BangkokSurasak Saokaew, Phayao

Turkey

Nese Demirturk, AfyonkarahisarNilüfer Ozabaci, Eskisehir Ilke Sipahi, Istanbul

United Kingdom

Omar M Aboumarzouk, WalesAbeer Al-Namankany, LondonErnest A Azzopardi, CardifUmberto Benedetto, CambridgeJoanne Brooke, London Noriko Cable, LondonDavid Chan, Cardiff YC Cheong, SouthamptonAndrew Currie, HarrowG Nabi, Dundee

WJMA|www.wjgnet.com III May 26, 2013

Lesley A Anderson, BelfastValentina Gallo, LondonGianpiero Gravante, Leicester Peter N Lee, Surrey Igho Onakpoya, Oxford Ashish Pradhan, HuntingdonEvridiki Patelarou, LondonJian-Qing Shi, NewcastleSurendra P Singh, Wolverhampton Natalie Taylor, LeedsYousef Shahin, HullZheng Ye, Cambridge

United States

L Joseph Su, RockvilleOlusola Adesope, PullmanMike Allen, MilwaukeeBhupinder Anand, BellaireStephen Aronoff, PhiladelphiaKoKo Aung, San AntonioWilliam L Baker, FarmingtonMoritz C Wyler von Ballmoos, MilwaukeeMatthew L Bechtold, ColumbiaAtul Bhardwaj, HersheySomjot S Brar, Los Angeles

Hui Cai, NashvilleSubhash Chandra, TowsonWen-Pin Chang, OmahaYong Chen, North WalesMyunghan Choi, PhoenixJohn Coverdale, HoustonPrakash C Deedwania, FresnoEugene Demidenko, HanoverHong-Wen Deng, New OrleansEric M Deshaies, SyracuseTao Fan, Whitehouse StationShinga Feresu, BloomingtonJanvier Gasana, MiamiKaveh Hajifathalian, BostonMohammad Obaidul Hoque, BaltimoreLarissa R Brunner Huber, CharlotteImran H Iftikhar, ColumbiaVijayvel Jayaprakash, BuffaloXuezhi Jiang, Weat ReadingShuo Jiao, SeattleEvelyn Johnson, BoiseLe Kang, Silver SpringSR Kapadia, ClevelandLior Katz, Houston Daniel M Laskin, RichmondYu Liang, Foster CityPaul Ellis Marik, Norfolk

Lynne V McFarland, SeattleMarcovalerio Melis, New YorkBrian J Miller, AugustaPavlos Msaouel, New YorkJoshua E Muscat, HersheyChee Yuan Ng, Loma LindaNghi C Nguyen, Saint LouisBrandi S Niemeier, WhitewaterThomas D Parsons, DentonNidal Abi Rafeh, New OrleansPraveen Roy, MarshfieldAli Salavati, PhiladelphiaAnkur Sethi, ChicagoTatyana A Shamliyan, MinneapoliQian Shi, RochesterZhongjie Shi, PhiladelphiaParam Puneet Singh, ChicagoKV Slavin, ChicagoAli El Solh, BuffaloJielin Sun, Winston-SalemRichard G Trohman, ChicagoLaurah Turner, CincinnatiSheila Wilhelm, DetroitAlex K Wong, Los AngelesXiaohui Xu, GainesvilleLu Yin, Nashville

WJMA|www.wjgnet.com IV May 26, 2013

World Journal ofMeta-AnalysisW J M A

Contents

IWJMA|www.wjgnet.com February 26, 2016|Volume 4|Issue 1|

Bimonthly Volume 4 Number 1 February 26, 2016

META-ANALYSIS1 Expressionofepithelialcellularadhesionmoleculeingastriccancer:Ameta-analysis

Xiao YB, Xi HQ, Li JY, Chen L

ContentsWorld Journal of Meta-Analysis

Volume 4 Number 1 February 26, 2016

EDITORS FOR THIS ISSUE

Responsible Assistant Editor: Xiang Li Responsible Science Editor: Fang-Fang Ji Responsible Electronic Editor: Ya-Jing Lu Proofing Editorial Office Director: Xiu-Xia SongProofing Editor-in-Chief: Lian-Sheng Ma

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PUBLICATIONDATEFebruary 26, 2016

COPYRIGHT© 2016 Baishideng Publishing Group Inc. Articles

published by this Open-Access journal are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited, the use is non commercial and is otherwise in compliance with the license.

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IIWJMA|www.wjgnet.com

ABOUT COVER

AIM AND SCOPE

INDExINg/ABSTRACTINg

FLYLEAF

February 26, 2016|Volume 4|Issue 1|

NAMEOFJOURNALWorld Journal of Meta-Analysis

ISSNISSN 2308-3840 (online)

LAUNCHDATEMay 26, 2013

FREQUENCYBimonthly

EDITOR-IN-CHIEFGiuseppe Biondi-Zoccai, MD, Assistant Professor, Department of Medico-Surgical Sciences and Biotech-nologies, Sapienza University of Rome, Latina 04100, Italy

EDITORIALOFFICEJin-Lei Wang, DirectorXiu-Xia Song, Vice DirectorWorld Journal of Meta-AnalysisRoom 903, Building D, Ocean International Center,

EditorialBoardMemberofWorldJournalofMeta-Analysis ,Yung-ChengSu,MD,

AttendingDoctor,Lecturer,DepartmentofEmergency,BuddhistTzuChiDalin

GeneralHospital,ChiayiCounty622,Taiwan

World Journal of Meta-Analysis (World J Meta-Anal, WJMA, online ISSN 2308-3840, DOI: 10.13105) is a peer-reviewed open access academic journal that aims to guide clinical practice and improve diagnostic and therapeutic skills of clinicians, with a specific focus on meta-analysis, systematic review, mixed-treatment comparison, meta-regression, overview of reviews.

WJMA covers a variety of clinical medical fields including allergy, anesthesiology, cardiac medicine, clinical genetics, clinical neurology, critical care, dentistry, dermatology, emergency medicine, endocrinology, family medicine, gastroenterology and hepatology, geriatrics and gerontology, hematology, immunology, infectious diseases, internal medicine, obstetrics and gynecology, oncology, ophthalmology, orthopedics, otolaryngology, pathology, pediatrics, peripheral vascular disease, psychiatry, radiology, rehabilitation, respiratory medicine, rheumatology, surgery, toxicology, transplantation, and urology and nephrology, while maintaining its unique dedication to systematic reviews and meta-analyses.

World Journal of Meta-Analysis is now indexed in Emerging Sources Citation Index (Web of

Science).

I-IV EditorialBoard

Expression of epithelial cellular adhesion molecule in gastric cancer: A meta-analysis

Yi-Bin Xiao, Hong-Qing Xi, Ji-Yang Li, Lin Chen

Yi-Bin Xiao, Hong-Qing Xi, Ji-Yang Li, Lin Chen, Department of General Surgery, Chinese People’s Liberation Army General Hospital, Beijing 100853, China

Author contributions: Xiao YB and Xi HQ contributed equally to this work; Xiao YB and Chen L designed the research; Xiao YB and Xi HQ collected and analyzed the data; Xiao YB wrote and revised the manuscript; Li JY provided analytic tools and checked the accuracy of the data.

Supported by The National High Technology Research and Development Program of China, No. 2012AA02A504.

Conflict-of-interest statement: The authors have no conflicts of interest to declare.

Data sharing statement: No additional data are available.

Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

Correspondence to: Lin Chen, MD, Professor, Department of General Surgery, Chinese People’s Liberation Army General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China. [email protected]: +86-10-66938128Fax: +86-10-68181689

Received: August 23, 2015Peer-review started: September 3, 2015First decision: November 13, 2015Revised: December 1, 2015Accepted: January 29, 2016Article in press: January 31, 2016Published online: February 26, 2016

AbstractAIM: To obtain an accurate evaluation of the association between high expression of epithelial cellular adhesion molecule (EpCAM) and gastric cancer (GC) risk.

METHODS: Studies that had examined the association between high expression of EpCAM and GC risk were identified by searching electronic databases PubMed, EMBASE, Cochrane library and Chinese Biomedical Literature database. Risk ratios (RRs) together with their 95%CIs were used to assess the association between high expression of EpCAM and GC risk. We selected eligible studies based on inclusion criteria. RevMan 5.3 software was used to calculate the pooled values.

RESULTS: A total of 14 studies were included in this meta-analysis. EpCAM-positive cases were significantly associated with tumor size (RR: 1.68, 95%CI: 1.47-1.91, P < 0.00001 fixed-effect), depth of invasion (RR: 1.37, 95%CI: 1.11-1.68, P = 0.003 random-effect), TNM stage (RR: 2.02, 95%CI: 1.35-3.02, P = 0.0007 random-effect), tumor location (RR: 0.80, 95%CI: 0.71-0.91, P = 0.0007 fixed-effect), histologic differentiation (RR: 1.23, 95%CI: 1.13-1.33, P < 0.00001 fixed-effect) and lymph node metastasis (RR: 1.89, 95%CI: 1.28-2.80, P = 0.001 random-effect). However, we did not observe any significant association between the presence of EpCAM with age, gender, distant metastasis, Borrmann type or Lauren classification. Additionally, EpCAM expression was not associated with the overall survival rate. The pooled HR of the overall effect was 1.39 (95%CI: 0.30-6.48, P = 0.67 random-effect).

CONCLUSION: Our meta-analysis indicates that EpCAM contributes to GC risk, which acts as a prognostic factor and a marker of poor outcome.

Key words: Epithelial cellular adhesion molecule; Gastric cancer; Prognosis; Progression; Meta-analysis

META-ANALYSIS

� February 26, 20�6|Volume 4|Issue �|WJMA|www.wjgnet.com

World Journal ofMeta-AnalysisW J M A

Submit a Manuscript: http://www.wjgnet.com/esps/Help Desk: http://www.wjgnet.com/esps/helpdesk.aspxDOI: �0.�3�05/wjma.v4.i�.�

World J Meta-Anal 20�6 February 26; 4(�): �-9ISSN 2308-3840 (online)

© 20�6 Baishideng Publishing Group Inc. All rights reserved.

© The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.

Core tip: This meta-analysis aimed to obtain an accurate evaluation of the association between high expression of epithelial cellular adhesion molecule (EpCAM) and gastric cancer (GC) risk. EpCAM-positive cases were significantly associated with tumor size, depth of invasion, TNM stage, tumor location, histologic differentiation and lymph node metastasis. EpCAM contributed to GC risk, and acted as a prognostic factor and a marker of poor outcome.

Xiao YB, Xi HQ, Li JY, Chen L. Expression of epithelial cellular adhesion molecule in gastric cancer: A meta-analysis. World J Meta-Anal 2016; 4(1): 1-9 Available from: URL: http://www.wjgnet.com/2308-3840/full/v4/i1/1.htm DOI: http://dx.doi.org/10.13105/wjma.v4.i1.1

INTRODUCTIONAlthough gastric cancer (GC) rates have decreased substantially in the past few decades, it remains the second most common cause of cancer-related death worldwide[1]. Patients with GC have a poor prognosis, especially those with advanced stage disease. The most common cause of this phenomenon is the advanced stage of most cases at the time of initial diagnosis. Additionally, tumor cell spread has occurred in some cases[1,2]. Currently, surgery is the primary treatment strategy for localized advanced GC, with an average 5-year survival rate of 20%-30%; however, for un-resectable disease such as metastatic or recurrent GC, chemotherapy is regarded as a basic therapeutic approach[1].

The efficacy of current chemotherapeutic agents is still unsatisfactory and these agents with poor specificity have significant side effects. Consequently, multimodality therapy options are needed to improve the prognosis of GC. This necessitates finding new adjuvant therapeutic targets and prognostic markers for GC patients.

The epithelial cellular adhesion molecule (EpCAM) is a 37-42 KDa, 314-amino-acid type I transmembrane glycoprotein with two epidermal growth factor-like repeats in the external domain and two α-actin binding sites for actin cytoskeleton linkage in the intracellular domain[2]. The 9-exon gene TACSTD1, which has been mapped to chromosome 2p21, encodes it. EpCAM functions as a homotypic intracellular adhesion molecule. It is interconnected with E-cadherin during the process of epithelial cell adhesion[2,3].

EpCAM is expressed in most normal epithelial tissues on the basolateral membrane and overexpression of EpCAM has been detected in a variety of epithelial cancers[4]. EpCAM was found to be overexpressed in colon cancer tissues, breast cancer squamous cells, ovarian carcinomas and most human adenocarcinomas.

Because its overexpression has effects on differentiation, cell proliferation, signaling and migration, EpCAM can be used as a marker to predict recurrence and metastasis of the tumor and influence survival of cancer patients[5].

Furthermore, EpCAM has been considered as a target antigen for a number of specific immunotherapies because of its frequent and high-level expression[6,7]. Catumaxomab, an EpCAM monoclonal antibody, has been used for the intraperitoneal treatment of malignant effusion in patients with EpCAM-positive cells since 2009. Catumaxomab also had a significant overall survival (OS) benefit in GC patients[8]. However, the role of EpCAM in GC is still unclear. Although several studies showed high expression of EpCAM in GC[6-10], which was related to cancer progression and survival prognosis, there is no comprehensive study on the correlation of EpCAM expression with survival prognosis or the effects of EpCAM expression on clinicopathologic characteristics in GC patients. Thus, this meta-analysis was conducted to determine the association between high expression of EpCAM and clinicopathological features and progression as well as prognosis of GC.

MATERIALS AND METHODSLiterature search strategyWe conducted a comprehensive literature search in PubMed, EMBASE, Cochrane library and Chinese Biom-edical Literature databases. There was no restriction on time period, sample size, population or languages. The search terms included “Stomach Neoplasms” OR “Gastric Neoplasms” OR “Stomach Cancer” OR “GC” OR “Stomach Carcinoma” OR “Gastric Carcinoma” AND “EpCAM” OR “epithelial cellular adhesion molecule”. The search was limited to studies in humans. All eligible studies were retrieved and their references were scanned for other relevant studies. Two reviewers (Yi-Bin Xiao and Hong-Qing Xi) independently screened titles and abstracts of all citations. When multiple articles were reported on the same or overlapping data, we selected the study that investigated the most individuals or the most recent study.

Inclusion and exclusion criteriaArticles were considered if: (1) they provided information on GC verified by pathological examination; (2) they provided information on case control or cohort studies that evaluated the association between EpCAM expression and GC; (3) no preoperative chemotherapy and/or radiotherapy was administered to patients; (4) they had available data for estimating risk ratio (RR) (95%CI); and (5) the control population did not contain patients with malignant tumors.

Studies were excluded if they: (1) had no control population; (2) were duplicates of an earlier publication; (3) reported insufficient data; (4) had cell or animal experiments; and (5) were letters, reviews, case reports and conference abstracts without original data or articles

Xiao YB et al . Epithelial cellular adhesion molecule in gastric cancer

2 February 26, 20�6|Volume 4|Issue �|WJMA|www.wjgnet.com

published in a book.

Data extractionTwo investigators (Yi-Bin Xiao and Hong-Qing Xi) reviewed all articles. Then the first investigator extracted the following information according to the prespecified selection criteria: (1) Publication details, including first author’s name, year of publication and publication journal; (2) Characteristics of the studied population, including country, ethnicity, number of cases and controls; and (3) Number and characteristics of different clinical and pathologic parameters of both the gastric patients and their control group, including age, gender, tumor size, depth of invasion, TNM stage, tumor location, distant metastasis, Borrmann type, Lauren classification, histologic differentiation and lymph node metastasis.

Discrepancies between the two investigators were resolved through consensus discussion.

Quality assessmentThe quality of the studies was assessed according to the Newcastle-Ottawa Scale (NOS) by two investigators (Yi-Bin Xiao and Hong-Qing Xi) independently. The scale includes three major classifications: Selection, com-parability and outcome. A maximum score of 1 was graded for each item, except for comparability, where a score of 2 was allowed to be graded. Scores ranged from 0 (lowest) to 9 (highest) and studies that scored equal to or higher than 7 points were assigned as “high-quality” studies, whereas those with scores less than 7 were considered “low-quality” studies. Any disagreement was resolved through consensus discussion.

Statistical analysisThe association between EpCAM and GC risk was evaluated using hazard ratio (HR, 95%CIs) for time-to-event data (OS) and (RR, 95%CIs) for dichotomous data (various adverse events). Cochran’s χ2-based Q test and Higgins I2 statistics were used to check heterogeneity among studies. I2 lay between 0 and 10%, and a value of 0% meant no observed heterogeneity, with larger values indicating increasing heterogeneity. P < 0.05 or I2 >50% was considered statistically significant. A value of 0% indicated no observed heterogeneity, and larger values showed increasing heterogeneity, with 25% indicating low, 50% indicating moderate, and 75% indicating high heterogeneity (Higgins, Thompson, Deeks, and Altman, 2003).

We selected the fixed-effect model (the Mantel-Haenszel method) if there was no significant heterogeneity. Otherwise, we selected the random-effect model (the DerSimonian and Laird method) if heterogeneity existed and could not be explained or corrected. Begg’s funnel plots were used to examine potential publication bias in this study. For the pooled analysis of the correlation between EpCAM expression and clinicopathological features, RRs and their 95%CIs were used to assess the effect. All the statistical tests were performed using

RevMan5.3 (Cochrane collaboration, Oxford, United Kingdom) software. Kaplan-Meier curves were read using an Engauge Digitizer 4.1. P < 0.05 was considered statistically significant. HRs or RRs > 1 meant a worse prognosis for GC patients with EpCAM overexpression and were considered to be statistically significant if the 95%CI did not overlap 1. In addition, sensitivity analysis was conducted by sequential omission of individual studies to evaluate the stability of the results.

RESULTSLiterature search and characteristicsA flow diagram of the literature search is shown in Figure 1. The initial search yielded a total of 190 studies according to the search criteria. A total of 28 potential relevant studies were recruited into this meta-analysis. Of these studies, three were excluded because they contained overlapping data. Another 11 studies were excluded because they were unable to offer EpCAM-specific data for calculating HRs or RRs according to the described method. A total of 14 studies that met the inclusion and exclusion criteria were included. Three studies reported an association between EpCAM and the 5-year survival rate[7,11,12], and 13 studies[1-11,13,14] were chosen to demonstrate the connection between EpCAM expression and clinical features. As a result, we did not find any additional articles using a manual search of references cited in the published studies. The details of the articles are summarized in Tables 1 and 2.

Correlation of EpCAM with clinicopathological parametersThirteen studies reported correlations between EpCAM expression and some clinical characteristics of GC (including age, gender, tumor size, depth of invasion, TNM stage, tumor location, distant metastasis, Borrmann type, Lauren classification, histologic differentiation and lymph node metastasis). These were pooled to calculate the RRs.

In our study, the expression level of EpCAM was higher in samples of GC than in normal ones (pooled RR = 2.16, 95%CI: 1.54-3.03, P < 0.00001 random-effect) (Figure 2A). In addition, EpCAM expression was significantly associated with tumor size (pooled RR = 1.68, 95%CI: 1.47-1.91, P < 0.00001 fixed-effect) (Figure 2B), depth of invasion (pooled RR = 1.37, 95%CI: 1.11-1.68, P = 0.003 random-effect) (Figure 2C), TNM stage (pooled RR = 2.02, 95%CI: 1.35-3.02, P = 0.0007 random-effect) (Figure 2D), tumor location (pooled RR = 0.80, 95%CI: 0.71-0.91, P = 0.0007 fixed-effect) (Figure 2E), histologic differentiation (pooled RR: 1.23, 95%CI: 1.13-1.33, P < 0.00001 fixed-effect) (Figure 2F), and lymph node metastasis (pooled RR = 1.89, 95%CI: 1.28-2.80, P = 0.001 random-effect) (Figure 2G). However, EpCAM expression in GC was not associated with age (pooled RR = 1.12, 95%CI: 0.93-1.35, P = 0.24 fixed-effect), gender (pooled RR =



was used to examine publication bias (Figure 3). We inspected its asymmetry visually and found that there was almost no potential for publication bias.

Sensitivity analysisOne included study was excluded at each time to inv-estigate the influence of the individual data on the overall results. The pooled RR or HR estimates were recalculated for the remaining studies. The statistical significance of the overall results was not changed when any individual study was excluded, which indicates the reliability of our results.

DISCUSSIONIn recent years, many cell adhesion molecules (CAMs) have proven to be responsible for tumorigenesis and metastasis[2,3]. The role of EpCAM is not only limited

0.97, 95%CI: 0.91-1.04, P = 0.37 fixed-effect), distant metastasis (pooled RR = 2.25, 95%CI: 0.77-6.61, P = 0.14, random-effect), Borrmann type (pooled RR = 1.03, 95%CI: 0.89-1.19, P = 0.70 fixed-effect), or Lauren classification (pooled RR = 1.64, 95%CI: 0.75-3.60, P = 0.21 random-effect).

Impact of EpCAM expression on OS in GC patientsMeta-analysis of the association between EpCAM expression and OS was determined in three studies. The pooled RR was analyzed using previously described methods. EpCAM expression was not associated with the OS rate. The pooled HR of the overall effect was 1.39 (95%CI: 0.30-6.48, P = 0.67) in the random-effect model (Figure 2H).

Assessment of publication bias The funnel plot test recommended for meta-analyses

Table 2 Raw data from each included study


Table 1 Characteristics of included studies

First author Country Year Ethnics Age (< 50: ≥50)

No. of patients (male:female)

No. of patients (EpCAM+: EpCAM-)

Diagnosis of GC (Histo-, Patho-, NR)

Study quality (NOS)

Zhang et al China 20�� Asian ��:3� 24:�8 34:8 Patho- 8Sun et al China 20�0 Asian 3�:29 48:�2 46:�4 Patho- 8Fang et al China 20�0 Asian 27:3� 39:�9 46:�2 Patho- 8Lu et al China 20�� Asian 43:48 70:2� 84:7 Patho- 9Yang et al China 20�4 Asian 33:39 57:�5 48:24 Patho- 9Peng et al China 20�� Asian 20:�� 8:�3 2�:�0 Patho- 9Yang et al China 20�2 Asian 33:62 66:29 56:39 Patho- 8Zhang et al China 20�4 Asian �7:25 24:�8 37:5 Patho- 7Li et al China 20�2 Asian NR 3��:�25 �79:257 Patho- 7Du et al China 2009 Asian 26:74 6�:39 74:26 Patho- 8Went et al Switzerland 2006 Caucasian NR 3��:��7 NR Patho- 7Kroepil et al Germany 20�3 Caucasian NR NR �26:37 Patho- 8Wang et al China 20�3 Asian NR 428:�73 247:354 NR 8Songun et al The Netherlands 2005 Caucasian NR NR NR Patho- 7

Histo-: Histology; Patho-: Pathology; NR: Not reported; NOS: Newcastle-Ottawa Scale classification; EpCAM: Epithelial cellular adhesion molecule.

First author Tumor size (≤ 5 cm:> 5 cm)

Depth of invasio-n (T1-T2: T3-T4)

TNM stage (Ⅰ-Ⅱ:Ⅲ-Ⅳ)

Tumor location (upper:middle:lower)

Distant metastasis (yes: no)

Borrma-nn type (Ⅰ:Ⅱ:Ⅲ:Ⅳ)

Lauren classificatio-n (intestinal:diffuse: mixed)

Histologic differentiate-on (high: moderate: low)

Lymph node metastasis (N0: N1/2/3)

Zhang et al NR2 NR NR NR 23:�9 8:�2:22 20:22Sun et al NR ��:49 NR NR NR NR NR 20:20:20 NRFang et al NR �7:4� �7:4� NR �8:40 NR NR ��:�7:30 �5:43Lu et al 4�:50 �9:72 34:57 4�:25:25 NR 8:�2:59:�� NR 3:24:64 3�:60Yang et al 45:27 35:37 35:37 NR NR NR NR NR 25:47Peng et al NR �9:�2 �9:�2 �2:�3:6 NR NR NR �5:�3:3 NRYang et al NR 7:88 NR 29:26:40 NR 3:�2:6�:�9 NR 6:�9:70 29:66Zhang et al �4:28 �3:29 �3:29 NR NR NR NR �6:26:0 ��:3�Li et al 256:�80 �66:270 �94:242 55:�63:2�8 6�:375 NR 223:2�3:0 �4�:295 �66:270Du et al NR NR NR NR NR NR 9�:�9 25:42:33 50:50Went et al NR 42:372 NR NR 25:445 NR NR NR �53:3�6Kroepil et al NR �07:56 NR NR 9:�54 NR 62:6�:40 NR 4�:�22Wang et al 350:25� 22�:380 262:339 84:223:294 9�:5�0 NR 299:302 �7:�75:409 220:38�Songun et al� NR NR NR NR NR NR NR NR NR

�Article written by Songun et al. only provided OS data; 2NR: Not reported.


to cell adhesion but is also involved in other cellular processes including signaling, cell migration, proliferation and differentiation[15]. EpCAM is a potent signal transducer, which can use components of the Wnt pathway and is involved in the regulation of cell proliferation and cell cycle progression[5,13,16]. It is overexpressed in many solid cancers including esophageal, pancreatic, prostate and gastric[12,17], and it has recently been identified as a type of cancer stem cell marker[14,18,19].

Identification of a prognostic factor such as EpCAM is necessary for high-risk patients for whom specific therapy might be necessary[20,21]. However, conflicting

data on the prognostic impact of EpCAM have been reported. Wenqi et al[22] reported that EpCAM was overexpressed in gastric cell lines and tumor tissues and downregulation of EpCAM resulted in a decrease in cell proliferation and suppressed tumor formation. In contrast, Songun et al[23] reported that 93% of 300 GC patients were EpCAM-positive and the loss of EpCAM expression indicated tumor aggression, especially in patients with stage Ⅰ and Ⅱ disease. Thus, the prognostic role of EpCAM in GC is still unclear and the association between clinical characteristics of GC patients and EpCAM expression levels needs to be further elucidated. These conflicting data were likely due to the small sample size and intratumoral heterogeneity of GC, which was observed in the studies.

This meta-analysis is the first study to systematically estimate EpCAM expression and its relationship with clinicopathological characteristics and OS rates in GC patients. We calculated pooled RRs to study the correlation of EpCAM with patient clinical characteristics. This showed that EpCAM expression was positively related with poor histological type, lymph node metastasis, high-grade of TNM stage and tumor size (> 5 cm), depth of invasion (T3-T4) and tumor location (lower part of the stomach) in GC patients. This suggests that GC patients with the above-mentioned clinical characteristics were more likely to have a poorer prognosis after the diagnosis was made.

The biological function of EpCAM may be implicated in the relationship between EpCAM expression and cancer outcome mentioned above. Recently, studies have reported that overexpression of EpCAM occurs in a variety of cancers, for example colon, breast and ovarian, and most human adenocarcinomas. Furthermore, it has effects on differentiation, proliferation and migration of cancer cells.

There are certain limitations in the present meta-analysis that need to be pointed out. First, although we tried to avoid biases in performing this meta-analysis, publication bias may have occurred because only publ-ished studies were included in the meta-analysis even if the statistical test did not show it. Second, we did not find any significant association between EpCAM expression and OS in GC patients. It is very likely that limited research has been done on EpCAM and its relationship with prognosis. Only three studies were included in the OS meta-analysis, with a relatively small sample size of 831 patients. Finally, there was heterogeneity between studies present in this article, with a P-value < 0.05, especially in the evaluation of the relationship between EpCAM expression and some adverse clinical parameters. This was related to insufficient sample size and a lack of certain original data. To adjust for this, we used a trim-and-fill method in the random-effect model to make the outcomes statistically credible.

In conclusion, this meta-analysis suggests that the expression of EpCAM is associated with poor clinico-pathological features of GC. However, because of the heterogeneity of included studies and bias of meta-analysis, our conclusions need to be interpreted with caution. More


Additional records identified through other sources (n = 0)

Records identified through database searching (n = 190)

Records after duplicates removed (n = 85)

Records excluded (n = 60) Letters, reviews, case reports and conference abstracts (n = 26) Animal or cell studies (n = 6) Not related to research topic (n = 28)

Records screened (n = 25)

Full-text articles assessed for eligibility (n = 14)

Full-text articles excluded (n = 11, not available data)

Studies included in qualitative synthesis (n = 14)

Studies included in qualitative synthesis (meta-analysis) (n = 14)

Figure 1 Study selection.


Experimental Control Risk ratio Risk ratioStudy or subgroup Events Total Events Total Weight M-H, Random, 95%CI M-H, Random, 95%CIJia-jia Yang 2014 33 48 4 24 10.5% 4.13 [1.65, 10.30]Li Li 2012 157 179 85 257 22.0% 2.65 [2.21, 3.18]Ming-dian Lu 2011 31 66 16 25 18.9% 0.73 [0.50, 1.08]Wang-qing Zhang 2014 28 37 1 5 4.3% 3.78 [0.65, 22.05]Yuan-Yu Wang 2013 220 247 119 354 22.3% 2.65 [2.27, 3.09]Yun-xiang Peng 2011 10 21 2 10 6.6% 2.38 [0.64, 8.90]Zhi-xue Fang 2010 35 46 6 12 15.4% 1.52 [0.84, 2.74]

Total (95%CI) 644 687 100.0% 2.02 [1.35, 3.02]Total events 514 233Heterogeneity: Tau2 = 0.18; χ 2 = 42.27, df = 6 (P < 0.00001); I 2 = 86%Test for overall effect: Z = 3.41 (P = 0.0007)

Experimental Control Risk ratio Risk ratioStudy or subgroup Events Total Events Total Weight M-H, Random, 95%CI M-H, Random, 95%CIFeride Kroepil 2013 44 126 12 37 7.5% 1.08 [0.64, 1.82]Jia-jia Yang 2014 41 48 15 24 10.6% 1.37 [0.98, 1.90]Li Li 2012 149 179 121 257 13.5% 1.77 [1.53, 2.04]Ming-dian Lu 2011 52 66 20 25 12.2% 0.98 [0.78, 1.24]P Went 2016 282 305 32 37 13.6% 1.07 [0.94, 1.22]Shi-bin Yang 2012 55 56 33 39 13.6% 1.16 [1.01, 1.33]Wang-qing Zhang 2014 28 37 1 5 1.3% 3.78 [0.65, 22.05]Xiao-tong Sun 2010 41 46 8 14 8.4% 1.56 [0.98, 2.48]Yuan-Yu Wang 2013 212 247 168 354 13.8% 1.81 [1.60, 2.04]Zhi-xue Fang 2010 36 46 5 12 5.6% 1.88 [0.95, 3.73]


Favours [experimental] Favours [control]0.01 0.1 1 10 100

Experimental Control Risk ratio Risk ratioStudy or subgroup Events Total Events Total Weight M-H, Fixed, 95%CI M-H, Fixed, 95%CIJia-jia Yang 2014 17 48 10 24 6.9% 0.85 [0.46, 1.56]Li Li 2012 100 179 80 257 34.2% 1.79 [1.44, 2.24]Ming-dian Lu 2011 38 66 12 25 9.1% 1.20 [0.76, 1.90]Wang-qing Zhang 2014 25 37 3 5 2.8% 1.13 [0.53, 2.38]Yuan-Yu Wang 2013 141 247 110 354 47.1% 1.84 [1.52, 2.22]

Total (95%CI) 577 665 100.0% 1.68 [1.47, 1.91]Total events 321 215Heterogeneity: χ 2 = 9.18, df = 4 (P = 0.06); I 2 = 56%Test for overall effect: Z = 7.69 (P < 0.00001)

A


Experimental Control Risk ratio Risk ratioStudy or subgroup Events Total Events Total Weight M-H, Random, 95%CI M-H, Random, 95%CIFeride Kroepil 2013 126 126 37 166 9.7% 4.44 [3.35, 5.88]Jia-jia Yang 2014 48 53 24 71 9.4% 2.68 [1.91, 3.75]Li Li 2012 179 221 257 307 10.3% 0.97 [0.89, 1.05]Ming-dian Lu 2011 84 95 7 75 7.1% 9.47 [4.66, 19.25]Shi-bin Yang 2012 56 60 39 60 10.0% 1.44 [1.18, 1.75]Wang-qing Zhang 2011 34 40 8 44 7.6% 4.67 [2.46, 8.87]Wang-qing Zhang 2014 30 31 12 36 8.7% 2.90 [1.82, 4.63]Xiao-tong Sun 2010 52 54 28 36 10.1% 1.24 [1.03, 1.49]Yuan-Yu Wang 2013 247 289 354 404 10.3% 0.98 [0.92, 1.04]Yun-xiang Peng 2011 21 27 10 27 8.3% 2.10 [1.23, 3.57]Zhi-xue Fang 2010 46 79 12 37 8.5% 1.80 [1.09, 2.96]

Total (95%CI) 1075 1263 100.0% 2.16 [1.54, 3.03]Total events 923 788Heterogeneity: Tau2 = 0.29; χ 2 = 375.56, df = 10 (P < 0.00001); I 2 = 97%Test for overall effect: Z = 4.45 (P < 0.00001)




B

C

D


Experimental Control Risk ratio Risk ratioStudy or subgroup Events Total Events Total Weight M-H, Fixed, 95%CI M-H, Fixed, 95%CIDu Wenqi 2008 30 74 3 26 1.1% 3.51 [1.17, 10.55]Jia-jia Yang 2014 36 48 9 24 3.1% 2.00 [1.16, 3.44]Li Li 2012 127 179 166 257 34.8% 1.10 [0.96, 1.25]Ming-dian Lu 2011 60 84 4 7 1.9% 1.25 [0.65, 2.41]Shi-bin Yang 2012 43 56 27 39 8.1% 1.11 [0.86, 1.43]Wang-qing Zhang 2011 21 34 1 8 0.4% 4.94 [0.78, 31.50]Wang-qing Zhang 2014 24 37 2 5 0.9% 1.62 [0.54, 4.87]Xiao-tong Sun 2010 17 46 3 14 1.2% 1.72 [0.59, 5.04]Yuan-Yu Wang 2013 180 247 227 354 47.7% 1.14 [1.02, 1.27]Yun-xiang Peng 2011 2 21 1 10 0.3% 0.95 [0.10, 9.30]Zhi-xue Fang 2010 29 46 1 12 0.4% 7.57 [1.14, 50.05]

Total (95%CI) 872 756 100.0% 1.23 [1.13, 1.33]Total events 569 444Heterogeneity: χ 2 = 18.48, df = 10 (P = 0.05); I 2 = 46%Test for overall effect: Z = 4.91 (P < 0.00001)



Experimental Control Risk ratio Risk ratioStudy or subgroup Events Total Events Total Weight M-H, Random, 95%CI M-H, Random, 95%CIDu Wenqi 2008 45 74 5 26 7.2% 3.16 [1.41, 7.10]Feride Kroepil 2013 92 125 29 37 10.1% 0.94 [0.77, 1.15]Jia-jia Yang 2014 35 48 12 24 9.1% 1.46 [0.94, 2.25]Li Li 2012 157 179 113 257 10.2% 1.99 [1.72, 2.31]Ming-dian Lu 2011 57 84 3 7 6.8% 1.58 [0.66, 3.77]P Went 2006 241 357 26 397 9.4% 10.31 [7.06, 15.05]Shi-bin Yang 2012 41 56 25 39 9.8% 1.14 [0.86, 1.52]Wang-qing Zhang 2011 19 30 3 12 6.1% 2.53 [0.92, 7.01]Wang-qing Zhang 2014 30 37 1 5 3.3% 4.05 [0.70, 23.56]Xiao-tong Sun 2010 31 46 6 14 8.1% 1.57 [0.83, 2.97]Yuan-Yu Wang 2013 220 247 161 354 10.2% 1.96 [1.73, 2.21]Zhi-xue Fang 2010 33 46 10 12 9.7% 0.86 [0.63, 1.18]



Hazard ratio Hazard ratioStudy or subgroup log [hazard ratio] SE Weight IV, Random, 95%CI IV, Random, 95%CII Songun 2005 -1.03 0.24 33.5% 0.36 [0.22, 0.57]Li Li 2012 1.61 0.26 33.3% 5.00 [3.01, 8.33]Shi-bin Yang 2012 0.42 0.27 33.2% 1.52 [0.90, 2.58]

Total (95%CI) 100.0% 1.39 [0.30, 6.48]Heterogeneity: Tau2 = 1.78; χ 2 = 56.20, df = 2 (P < 0.00001); I 2 = 96%Test for overall effect: Z = 0.42 (P = 0.67) Favours [experimental] Favours [control]

0.01 0.1 1 10 100

Experimental Control Risk ratio Risk ratioStudy or subgroup Events Total Events Total Weight M-H, Fixed, 95%CI M-H, Fixed, 95%CILi Li 2012 79 179 139 257 38.5% 0.82 [0.67, 1.00]Ming-dian Lu 2011 23 84 2 7 1.2% 0.96 [0.28, 3.25]Shi-bin Yang 2012 19 56 21 39 8.4% 0.63 [0.40, 1.01]Yuan-Yu Wang 2013 107 247 187 354 51.9% 0.82 [0.69, 0.98]

Total (95%CI) 566 657 100.0% 0.80 [0.71, 0.91]Total events 228 349Heterogeneity: Tau2 = 1.20, df = 3 (P = 0.75); I 2 = 0%Test for overall effect: Z = 3.40 (P = 0.0007) Favours [experimental] Favours [control]

0.01 0.1 1 10 100

E

F

G

H

Figure 2 Meta-analysis Forest plot. A: Meta-analysis Forest plot concerning the expression level of epithelial cellular adhesion molecule with gastric cancer between samples of gastric cancer and normal ones; B: Meta-analysis Forest plot concerning tumor size; C: Meta-analysis Forest plot concerning depth of invasion; D: Meta-analysis Forest plot concerning TNM stage; E: Meta-analysis Forest plot concerning tumor location; F: Meta-analysis Forest plot concerning histologic differentiation; G: Meta-analysis Forest plot concerning lymph node metastasis; H: Meta-analysis Forest plot concerning overall survival rate.


clinical studies will be required to determine the association between the expression of EpCAM and GC prognosis.

COMMENTSBackgroundAlthough gastric cancer (GC) rates have decreased substantially in the past few decades, it remains the second most common cause of cancer-related death worldwide. Although several studies showed high expression of epithelial cellular adhesion molecule (EpCAM) in GC, which was related to cancer progression and survival prognosis, there is no comprehensive study on the correlation of EpCAM expression with survival prognosis or the effects of EpCAM expression on clinicopathologic characteristics in GC patients.

Research frontiersThis meta-analysis was conducted to determine the association between high expression of EpCAM and clinicopathological features and progression as well as prognosis of GC.

Innovations and breakthroughsStudies that had examined the association between high expression of EpCAM and GC risk were identified by searching electronic databases PubMed, EMBASE, Cochrane library and Chinese Biomedical Literature database.

ApplicationsThis meta-analysis indicates that EpCAM contributes to GC risk, which acts as a prognostic factor and a marker of poor outcome.

Peer-reviewThe authors reported the “Expression of epithelial cellular adhesion molecule

in gastric cancer: A meta-analysis”. These findings are important to those with closely related research interests. It is well organized and systemically analysed.

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0.01 0.1 1 10 100RR

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Figure 3 Funnel plot of tumor size (A), tumor location (B) and histologic differentiation (C). RR: Risk ratio.

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P- Reviewer: Lee HW, Matsuo Y S- Editor: Wang JL L- Editor: A E- Editor: Lu YJ



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