title: Prognostic role and implications of mutation status of tumor suppressor gene ARID1A in cancer: a systematic review and meta-analysis.
abstract: Loss of the tumor suppressor gene AT-rich interactive domain-containing protein 1A (ARID1A) has been demonstrated in several cancers, but its prognostic role is unknown. We aimed to investigate the risk associated with loss of ARID1A (ARID1A-) for all-cause mortality, cancer-specific mortality and recurrence of disease in subjects with cancer. PubMed and SCOPUS search from database inception until 01/31/2015 without language restriction was conducted, contacting authors for unpublished data. Eligible were prospective studies reporting data on prognostic parameters in subjects with cancer, comparing participants with presence of ARID1A (ARID1A+) vs. ARID1A-, assessed either via immunohistochemistry (loss of expression) or with genetic testing (presence of mutation). Data were summarized using risk ratios (RR) for number of deaths/recurrences and hazard ratios (HR) for time-dependent risk related to ARID1A- adjusted for potential confounders. Of 136 hits, 25 studies with 5,651 participants (28 cohorts; ARID1A-: n = 1,701; ARID1A+: n = 3,950), with a mean follow-up period of 4.7 ± 1.8 years, were meta-analyzed. Compared to ARID1A+, ARID1A- significantly increased cancer-specific mortality (studies = 3; RR = 1.55, 95% confidence interval (CI) = 1.19-2.00, I(2) = 31%). Using HRs adjusted for potential confounders, ARID1A- was associated with a greater risk of cancer-specific mortality (studies = 2; HR = 2.55, 95%CI = 1.19-5.45, I(2) = 19%) and cancer recurrence (studies = 10; HR = 1.93, 95%CI = 1.22-3.05, I(2) = 76%). On the basis of these results, we have demonstrated that loss of ARID1A shortened time to cancer-specific mortality, and to recurrence of cancer when adjusting for potential confounders. For its role, this gene should be considered as an important potential target for personalized medicine in cancer treatment.
authors.affiliation: Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy.|Department of Pathology, The Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Claudio
authors.initials: C
authors.lastname: Luchini
authors.affiliation: Department of Medicine, Geriatrics Division, University of Padova, Padova, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Veronese
authors.affiliation: Department of Neurosciences, University of Padova, Padova, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Solmi
authors.affiliation: Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Hanbyoul
authors.initials: H
authors.lastname: Cho
authors.affiliation: Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Jae-Hoon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, St. Leonards, Australia.|Sydney Vital Translational Research Centre St. Leonards, Australia.|University of Sydney, Sydney, NSW, Australia.|Department of Anatomical Pathology, SYDPATH St. Vincent's Hospital, Sydney, NSW, Australia.
authors.forename: Angela
authors.initials: A
authors.lastname: Chou
authors.affiliation: Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, St. Leonards, Australia.|Sydney Vital Translational Research Centre St. Leonards, Australia.|University of Sydney, Sydney, NSW, Australia.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Gill
authors.affiliation: Department of Pathology, The Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Sheila F
authors.initials: SF
authors.lastname: Faraj
authors.affiliation: Department of Pathology, The Johns Hopkins University, Baltimore, MD, USA.|Centro para el Desarrollo de la Investigación Científica (CEDIC), Asunción, Paraguay.
authors.forename: Alcides
authors.initials: A
authors.lastname: Chaux
authors.affiliation: Department of Pathology, The Johns Hopkins University, Baltimore, MD, USA.
authors.forename: George J
authors.initials: GJ
authors.lastname: Netto
authors.affiliation: Department of Obstetrics and Gynecology, Shimane University School of Medicine, Shimane, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Nakayama
authors.affiliation: Department of Obstetrics and Gynecology, Shimane University School of Medicine, Shimane, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Kyo
authors.affiliation: Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, South Korea.
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Lee
authors.affiliation: Department of Surgery, Seoul National University Bundang Hospital, Seongnam, South Korea.
authors.forename: Duck-Woo
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Department of Laboratory Medicine and Keenan Research Centre, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: George M
authors.initials: GM
authors.lastname: Yousef
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Athens, Athens, Greece.
authors.forename: Andreas
authors.initials: A
authors.lastname: Scorilas
authors.affiliation: Department of Gynecologic Oncology, Tom Baker Cancer Centre, Calgary, Alberta, Canada.
authors.forename: Gregg S
authors.initials: GS
authors.lastname: Nelson
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Köbel
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Steve E
authors.initials: SE
authors.lastname: Kalloger
authors.affiliation: Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: David F
authors.initials: DF
authors.lastname: Schaeffer
authors.affiliation: Department of Systems Biology for Medicine of School of Basic Medical Sciences, and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Hai-Bo
authors.initials: HB
authors.lastname: Yan
authors.affiliation: Department of Systems Biology for Medicine of School of Basic Medical Sciences, and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Yokoyama
authors.affiliation: Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, China.
authors.forename: Xianyu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, China.
authors.forename: Da
authors.initials: D
authors.lastname: Pang
authors.affiliation: Department of Laboratory Medicine and Keenan Research Centre, Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Lichner
authors.affiliation: Department of Medicine, Geriatrics Division, University of Padova, Padova, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Sergi
authors.affiliation: Department of Medicine, Geriatrics Division, University of Padova, Padova, Italy.
authors.forename: Enzo
authors.initials: E
authors.lastname: Manzato
authors.affiliation: Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Capelli
authors.affiliation: Department of Pathology, The Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Laura D
authors.initials: LD
authors.lastname: Wood
authors.affiliation: Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Scarpa
authors.affiliation: The Zucker Hillside Hospital, Psychiatry Research, North Shore - Long Island Jewish Health System, Glen Oaks, New York, USA.|Hofstra North Shore LIJ School of Medicine, Hempstead, New York, USA.|The Feinstein Institute for Medical Research, Manhasset, New York, USA.|Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Christoph U
authors.initials: CU
authors.lastname: Correll
mesh_terms: D015331:Cohort Studies; D004268:DNA-Binding Proteins; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009369:Neoplasms / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics*; D011379:Prognosis; D014157:Transcription Factors / Q000235:genetics*
chemical_list: C112476:ARID1A protein, human; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors
keywords: ARID1A; SWI/SNF; chromatin remodeling; targeted therapy; tumor suppressor gene