Research Papers:
Prognostic role and implications of mutation status of tumor suppressor gene ARID1A in cancer: a systematic review and meta-analysis
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Abstract
Claudio Luchini1,2, Nicola Veronese3, Marco Solmi4, Hanbyoul Cho5, Jae-Hoon Kim5, Angela Chou6,7, Anthony J. Gill6, Sheila F. Faraj2, Alcides Chaux2,8, George J. Netto2, Kentaro Nakayama9, Satoru Kyo9, Soo Young Lee10, Duck-Woo Kim11, George M. Yousef12, Andreas Scorilas13, Gregg S. Nelson14, Martin Köbel15, Steve E. Kalloger16, David F. Schaeffer16, Hai-Bo Yan17, Feng Liu17, Yoshihito Yokoyama18, Xianyu Zhang19, Da Pang19, Zsuzsanna Lichner20, Giuseppe Sergi3, Enzo Manzato3, Paola Capelli1, Laura D. Wood2, Aldo Scarpa1, Christoph U. Correll21,22,23,24
1Department of Pathology and Diagnostics, University and Hospital Trust of Verona, Verona, Italy
2Department of Pathology, The Johns Hopkins University, Baltimore, MD, USA
3Department of Medicine, Geriatrics Division, University of Padova, Padova, Italy
4Department of Neurosciences, University of Padova, Padova, Italy
5Department of Obstetrics and Gynecology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
6Cancer Diagnosis and Pathology Group, Kolling Institute of Medical Research, St. Leonards, Australia, Sydney Vital Translational Research Centre St. Leonards Australia and University of Sydney, Sydney, NSW, Australia
7Department of Anatomical Pathology, SYDPATH St. Vincent’s Hospital, Sydney, NSW, Australia
8Centro para el Desarrollo de la Investigación Científica (CEDIC), Asunción, Paraguay
9Department of Obstetrics and Gynecology, Shimane University School of Medicine, Shimane, Japan
10Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, South Korea
11Department of Surgery, Seoul National University Bundang Hospital, Seongnam, South Korea
12Department of Laboratory Medicine and Keenan Research Centre, Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Toronto, Ontario, Canada
13Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Athens, Athens, Greece
14Department of Gynecologic Oncology, Tom Baker Cancer Centre, Calgary, Alberta, Canada
15Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, Alberta, Canada
16Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, British Columbia, Canada
17Department of Systems Biology for Medicine of School of Basic Medical Sciences, and Institutes of Biomedical Sciences, Fudan University, Shanghai, China
18Department of Obstetrics and Gynecology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan
19Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, China
20Department of Laboratory Medicine and Keenan Research Centre, Li Ka Shing Knowledge Institute of St. Michael’s Hospital, Toronto, Ontario, Canada
21The Zucker Hillside Hospital, Psychiatry Research, North Shore - Long Island Jewish Health System, Glen Oaks, New York, USA
22Hofstra North Shore LIJ School of Medicine, Hempstead, New York, USA
23The Feinstein Institute for Medical Research, Manhasset, New York, USA
24Albert Einstein College of Medicine, Bronx, New York, USA
Correspondence to:
Claudio Luchini, e-mail: [email protected], [email protected]
Keywords: ARID1A, SWI/SNF, chromatin remodeling, targeted therapy, tumor suppressor gene
Received: July 07, 2015 Accepted: August 27, 2015 Published: September 08, 2015
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, I2 = 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, I2 = 19%) and cancer recurrence (studies = 10; HR = 1.93, 95%CI = 1.22–3.05, I2 = 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.
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