Research Papers:

Prognostic role and implications of mutation status of tumor suppressor gene ARID1A in cancer: a systematic review and meta-analysis

Claudio Luchini _, Nicola Veronese, Marco Solmi, Hanbyoul Cho, Jae-Hoon Kim, Angela Chou, Anthony J. Gill, Sheila F. Faraj, Alcides Chaux, George J. Netto, Kentaro Nakayama, Satoru Kyo, Sun Young Lee, Duck-Woo Kim, George M. Yousef, Andreas Scorilas, Gregg S. Nelson, Martin Köbel, Steve E. Kalloger, David F. Schaeffer, Hai-Bo Yan, Feng Liu, Yoshihito Yokoyama, Xianyu Zhang, Da Pang, Zsuzsanna Lichner, Giuseppe Sergi, Enzo Manzato, Paola Capelli, Laura D. Wood, Aldo Scarpa and Christoph U. Correll

PDF  |  HTML  |  Supplementary Files  |  How to cite

Oncotarget. 2015; 6:39088-39097. https://doi.org/10.18632/oncotarget.5142

Metrics: PDF 3714 views  |   HTML 7650 views  |   ?  


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


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.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 5142