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, Soo Young Lee, Duck Woo Kim, George M. Yousef, Andreas Scorilas, Gregg S. Nelson, Martin Köbel, Steve E. Kalloger, David F. SchaefferHai Bo Yan, Feng Liu, Yoshihito Yokoyama, Xianyu Zhang, Da Pang, Zsuzsanna Lichner, Giuseppe Sergi, Enzo Manzato, Paola Capelli, Laura D. Wood, Aldo Scarpa, Christoph U. Correll

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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search from database inception until 01/31/2015 without language restriction was conducted, contacting authors for unpublished data.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.

Original languageEnglish
Pages (from-to)39088-39097
Number of pages10
JournalOncotarget
Volume6
Issue number36
DOIs
Publication statusPublished - 2015 Jan 1

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All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Luchini, C., Veronese, N., Solmi, M., Cho, H., Kim, J. H., Chou, A., Gill, A. J., Faraj, S. F., Chaux, A., Netto, G. J., Nakayama, K., Kyo, S., Lee, S. Y., Kim, D. W., Yousef, G. M., Scorilas, A., Nelson, G. S., Köbel, M., Kalloger, S. E., ... Correll, C. U. (2015). Prognostic role and implications of mutation status of tumor suppressor gene ARID1A in cancer: A systematic review and meta-analysis. Oncotarget, 6(36), 39088-39097. https://doi.org/10.18632/oncotarget.5142