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 Delong Wood, Aldo Scarpa, Christoph U. Correll

Research output: Contribution to journalArticle

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search from database inception until 01/31/2015 without language restriction was conducted, contacting authors for unpublished data.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 (US)
Pages (from-to)39088-39097
Number of pages10
JournalOncotarget
Volume6
Issue number36
DOIs
StatePublished - 2015

Fingerprint

Tumor Suppressor Genes
Meta-Analysis
Mutation
Neoplasms
Mortality
Recurrence
Confidence Intervals
Protein Domains
Odds Ratio
Precision Medicine
Genetic Testing
PubMed
Research Design
Language
Immunohistochemistry
Databases
Prospective Studies

Keywords

  • ARID1A
  • Chromatin remodeling
  • SWI/SNF
  • Targeted therapy
  • Tumor suppressor gene

ASJC Scopus subject areas

  • Oncology

Cite this

Prognostic role and implications of mutation status of tumor suppressor gene ARID1A in cancer : A systematic review and meta-analysis. / Luchini, Claudio; Veronese, Nicola; Solmi, Marco; Cho, Hanbyoul; Kim, Jae Hoon; Chou, Angela; Gill, Anthony J.; Faraj, Sheila F.; Chaux, Alcides; Netto, George J.; Nakayama, Kentaro; Kyo, Satoru; Lee, Soo Young; Kim, Duck Woo; Yousef, George M.; Scorilas, Andreas; Nelson, Gregg S.; Köbel, Martin; Kalloger, Steve E.; Schaeffer, David F.; Yan, Hai Bo; Liu, Feng; Yokoyama, Yoshihito; Zhang, Xianyu; Pang, Da; Lichner, Zsuzsanna; Sergi, Giuseppe; Manzato, Enzo; Capelli, Paola; Wood, Laura Delong; Scarpa, Aldo; Correll, Christoph U.

In: Oncotarget, Vol. 6, No. 36, 2015, p. 39088-39097.

Research output: Contribution to journalArticle

Luchini, C, Veronese, N, Solmi, M, Cho, H, Kim, JH, Chou, A, Gill, AJ, Faraj, SF, Chaux, A, Netto, GJ, Nakayama, K, Kyo, S, Lee, SY, Kim, DW, Yousef, GM, Scorilas, A, Nelson, GS, Köbel, M, Kalloger, SE, Schaeffer, DF, Yan, HB, Liu, F, Yokoyama, Y, Zhang, X, Pang, D, Lichner, Z, Sergi, G, Manzato, E, Capelli, P, Wood, LD, Scarpa, A & Correll, CU 2015, 'Prognostic role and implications of mutation status of tumor suppressor gene ARID1A in cancer: A systematic review and meta-analysis', Oncotarget, vol. 6, no. 36, pp. 39088-39097. https://doi.org/10.18632/oncotarget.5142
Luchini, Claudio ; Veronese, Nicola ; Solmi, Marco ; Cho, Hanbyoul ; Kim, Jae Hoon ; Chou, Angela ; Gill, Anthony J. ; Faraj, Sheila F. ; Chaux, Alcides ; Netto, George J. ; Nakayama, Kentaro ; Kyo, Satoru ; Lee, Soo Young ; Kim, Duck Woo ; Yousef, George M. ; Scorilas, Andreas ; Nelson, Gregg S. ; Köbel, Martin ; Kalloger, Steve E. ; Schaeffer, David F. ; Yan, Hai Bo ; Liu, Feng ; Yokoyama, Yoshihito ; Zhang, Xianyu ; Pang, Da ; Lichner, Zsuzsanna ; Sergi, Giuseppe ; Manzato, Enzo ; Capelli, Paola ; Wood, Laura Delong ; Scarpa, Aldo ; Correll, Christoph U. / Prognostic role and implications of mutation status of tumor suppressor gene ARID1A in cancer : A systematic review and meta-analysis. In: Oncotarget. 2015 ; Vol. 6, No. 36. pp. 39088-39097.
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AU - Luchini, Claudio

AU - Veronese, Nicola

AU - Solmi, Marco

AU - Cho, Hanbyoul

AU - Kim, Jae Hoon

AU - Chou, Angela

AU - Gill, Anthony J.

AU - Faraj, Sheila F.

AU - Chaux, Alcides

AU - Netto, George J.

AU - Nakayama, Kentaro

AU - Kyo, Satoru

AU - Lee, Soo Young

AU - Kim, Duck Woo

AU - Yousef, George M.

AU - Scorilas, Andreas

AU - Nelson, Gregg S.

AU - Köbel, Martin

AU - Kalloger, Steve E.

AU - Schaeffer, David F.

AU - Yan, Hai Bo

AU - Liu, Feng

AU - Yokoyama, Yoshihito

AU - Zhang, Xianyu

AU - Pang, Da

AU - Lichner, Zsuzsanna

AU - Sergi, Giuseppe

AU - Manzato, Enzo

AU - Capelli, Paola

AU - Wood, Laura Delong

AU - Scarpa, Aldo

AU - Correll, Christoph U.

PY - 2015

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N2 - 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.

AB - 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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KW - Chromatin remodeling

KW - SWI/SNF

KW - Targeted therapy

KW - Tumor suppressor gene

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