Skip to main content
SpringerLink
Log in

High Expression of AT-Rich Interactive Domain 3A (ARID3A) is Associated with Good Prognosis in Colorectal Carcinoma

  • Translational Research and Biomarkers
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

AT-rich interactive domain 3A (ARID3A) is a member of the ARID family of DNA-binding proteins. Previous reports have shown that ARID3A controls cell growth in a p53-dependent manner. Recently, it has been reported that expression of the ARID3A protein was markedly increased in colon cancer tissue compared with matched normal colonic mucosa. However, little is currently known about the role of ARID3A in colorectal cancer (CRC). The aim of this study was to investigate the clinical significance of ARID3A expression in CRC.

Methods

We examined ARID3A expression in 690 CRC patients using tissue microarray and immunohistochemistry. Kaplan–Meier analysis and Cox proportional hazard models were used to estimate the impact of ARID3A expression on overall survival.

Results

Of the 690 cases, 195 tumors were strongly positive for ARID3A, 187 were weakly positive, and 308 were negative. ARID3A expression in CRC was significantly correlated with age, degree of differentiation, depth of invasion, lymph node metastasis, distant metastasis, tumor–node–metastasis stage, status of microsatellite instability, and carcinoembryonic antigen levels. The overall survival of CRC patients with strong ARID3A expression was significantly longer than that of patients with weak or negative ARID3A expression. We also performed an additional survival analysis on 388 colon cancer patients and 302 rectal cancer patients. In doing so, a favorable prognostic effect of ARID3A expression was revealed only in the colon cancer group (p = 0.002), not in rectal cancer. Moreover, we showed that the effect of ARID3A on the survival was correlated with p53 status. Using multivariate analysis, we found that strong expression of ARID3A was an independent predictor for better prognosis in CRC.

Conclusions

Our data suggested that strong expression of ARID3A may predict a good prognosis in patients with CRC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

FIG. 1
FIG. 2
FIG. 3

Similar content being viewed by others

REFERENCES

  1. Kang UB, Yeom J, Kim HJ, Kim H, Lee C. Expression profiling of more than 3500 proteins of MSS-type colorectal cancer by stable isotope labeling and mass spectrometry. J Proteomics. 2012;75:3050–62.

    Article  CAS  PubMed  Google Scholar 

  2. Wilsker D, Patsialou A, Dallas PB, Moran E. ARID proteins: a diverse family of DNA binding proteins implicated in the control of cell growth, differentiation, and development. Cell Growth Differ. 2002;13:95–106.

    CAS  PubMed  Google Scholar 

  3. Wilsker D, Probst L, Wain HM, Maltais L, Tucker PW, Moran E. Nomenclature of the ARID family of DNA-binding proteins. Genomics. 2005;86:242–51.

    Article  CAS  PubMed  Google Scholar 

  4. Herrscher RF, Kaplan MH, Lelsz DL, Das C, Scheuermann R, Tucker PW. The immunoglobulin heavy-chain matrix-associating regions are bound by Bright: a B cell-specific trans-activator that describes a new DNA-binding protein family. Genes Dev. 1995;9:3067–82.

    Article  CAS  PubMed  Google Scholar 

  5. Rajaiya J, Nixon JC, Ayers N, Desgranges ZP, Roy AL, Webb CF. Induction of immunoglobulin heavy-chain transcription through the transcription factor Bright requires TFII-I. Mol Cell Biol. 2006;26:4758–68.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Webb CF, Smith EA, Medina KL, Buchanan KL, Smithson G, Dou S. Expression of bright at two distinct stages of B lymphocyte development. J Immunol. 1998;160:4747–54.

    CAS  PubMed  Google Scholar 

  7. Kortschak RD, Reimann H, Zimmer M, Eyre HJ, Saint R, Jenne DE. The human dead ringer/bright homolog, DRIL1: cDNA cloning, gene structure, and mapping to D19S886, a marker on 19p13.3 that is strictly linked to the Peutz–Jeghers syndrome. Genomics. 1998;51:288–92.

    Article  CAS  PubMed  Google Scholar 

  8. Nixon JC, Rajaiya JB, Ayers N, Evetts S, Webb CF. The transcription factor, Bright, is not expressed in all human B lymphocyte subpopulations. Cell Immunol. 2004;228:42–53.

    Article  CAS  PubMed  Google Scholar 

  9. Suzuki M, Okuyama S, Okamoto S, Shirasuna K, Nakajima T, Hachiya T, et al. A novel E2F binding protein with Myc-type HLH motif stimulates E2F-dependent transcription by forming a heterodimer. Oncogene. 1998;17:853–65.

    Article  CAS  PubMed  Google Scholar 

  10. Fukuyo Y, Mogi K, Tsunematsu Y, Nakajima T. E2FBP1/hDril1 modulates cell growth through downregulation of promyelocytic leukemia bodies. Cell Death Differ. 2004;11:747–59.

    Article  CAS  PubMed  Google Scholar 

  11. Peeper DS, Shvarts A, Brummelkamp T, Douma S, Koh EY, Daley GQ, et al. A functional screen identifies hDRIL1 as an oncogene that rescues RAS-induced senescence. Nat Cell Biol. 2002;4:148–53.

    Article  CAS  PubMed  Google Scholar 

  12. Ma K, Araki K, Ichwan SJ, Suganuma T, Tamamori-Adachi M, Ikeda MA. E2FBP1/DRIL1, an AT-rich interaction domain-family transcription factor, is regulated by p53. Mol Cancer Res. 2003;1:438–44.

    CAS  PubMed  Google Scholar 

  13. Lestari W, Ichwan SJ, Otsu M, Yamada S, Iseki S, Shimizu S, et al. Cooperation between ARID3A and p53 in the transcriptional activation of p21WAF1 in response to DNA damage. Biochem Biophys Res Commun. 2012;417:710–6.

    Article  CAS  PubMed  Google Scholar 

  14. Wang B, Xiao Z, Ren EC. Redefining the p53 response element. Proc Natl Acad Sci USA. 2009;106:14373–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Hilska M, Collan YU, O Laine VJ, Kössi J, Hirsimaki P, Laato M, et al. The significance of tumor markers for proliferation and apoptosis in predicting survival in colorectal cancer. Dis Colon Rectum. 2005;48:2197–208.

    Google Scholar 

  16. Watanabe T, Wu TT, Catalano PJ, Ueki T, Satriano R, Haller DG, et al. Molecular predictors of survival after adjuvant chemotherapy for colon cancer. N Engl J Med. 2001;344:1196–206.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Elsaleh H, Powell B, Soontrapornchai P, Joseph D, Goria F, Spry N, et al. p53 gene mutation, microsatellite instability and adjuvant chemotherapy: impact on survival of 388 patients with Dukes’ C colon carcinoma. Oncology. 2000;58:52–9.

    Article  CAS  PubMed  Google Scholar 

  18. Chen MF, Lee KD, Yeh CH, Chen WC, Huang WS, Chin CC, et al. Role of peroxiredoxin I in rectal cancer and related to p53 status. Int J Radiat Oncol Biol Phys. 2010;78:868–78.

    Article  CAS  PubMed  Google Scholar 

  19. Satow R, Shitashige M, Jigami T, Fukami K, Honda K, Kitabayashi I, et al. β-catenin inhibits promyelocytic leukemia protein tumor suppressor function in colorectal cancer cells. Gastroenterology. 2012;142:572–81.

    Article  CAS  PubMed  Google Scholar 

  20. Cabrera CM, Jimenez P, Concha A, Garrido F, Ruiz-Cabello F. Promyelocytic leukemia (PML) nuclear bodies are disorganized in colorectal tumors with total loss of major histocompatibility complex class I expression and LMP7 downregulation. Tissue Antigens. 2004;63:446–52.

    Article  CAS  PubMed  Google Scholar 

  21. Gurrieri C, Capodieci P, Bernardi R, Scaglioni PP, Nafa K, Rush LJ, et al. Loss of the tumor suppressor PML in human cancers of multiple histologic origins. J Natl Cancer Inst. 2004;96:269–79.

    Article  CAS  PubMed  Google Scholar 

  22. Webb CF, Bryant J, Popowski M, Allred L, Kim D, Harriss J, et al. The ARID family transcription factor bright is required for both hematopoietic stem cell and B lineage development. Mol Cell Biol. 2011;31:1041–53.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. An G, Miner CA, Nixon JC, Kincade PW, Bryant J, Tucker PW, et al. Loss of Bright/ARID3a function promotes developmental plasticity. Stem Cells. 2010;28:1560–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Ben-Porath I, Thomson MW, Carey VJ, Ge R, Bell GW, Regev A, Weinberg RA. An embryonic stem cell-like gene expression signature in poorly differentiated aggressive human tumors. Nat Genet. 2008;40:499–507.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Vaiopoulos AG, Kostakis ID, Koutsilieris M, Papavassiliou AG. Colorectal cancer stem cells. Stem Cells. 2012;30:363–71.

    Article  CAS  PubMed  Google Scholar 

  26. Saiki Y, Ishimaru S, Mimori K, Takatsuno Y, Nagahara M, Ishii H, et al. Comprehensive analysis of the clinical significance of inducing pluripotent stemness-related gene expression in colorectal cancer cells. Ann Surg Oncol. 2009;16:2638–44.

    Article  PubMed  Google Scholar 

  27. Saigusa S, Tanaka K, Toiyama Y, Yokoe T, Okugawa Y, Ioue Y, et al. Correlation of CD133, OCT4, and SOX2 in rectal cancer and their association with distant recurrence after chemoradiotherapy. Ann Surg Oncol. 2009;16:3488–98.

    Article  PubMed  Google Scholar 

Download references

Acknowledgment

This work was supported by the Mid-career Researcher Program (2012R1A2A2A01005196) through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology and by a grant of the Korean Health 21 R&D Project, Ministry of Health and Welfare, Republic of Korea (A111218-CP01).

Conflict of interest

No conflicts of interest are declared.

Author information

Authors and Affiliations

  1. Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea

    Meiying Song MD, PhD, Won Kyu Kim BS & Hoguen Kim MD, PhD

  2. Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea

    Meiying Song MD, PhD, Hyunki Kim MD, PhD, Won Kyu Kim BS & Hoguen Kim MD, PhD

  3. Division of Gastroenterology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea

    Sung Pil Hong MD, PhD

  4. Life Sciences Division, Korea Institute of Science and Technology, Seoul, Republic of Korea

    Cheolju Lee PhD

  5. Department of Biomolecular Science, University of Science and Technology, Taejon, Republic of Korea

    Cheolju Lee PhD

Authors
  1. Meiying Song MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hyunki Kim MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Won Kyu Kim BS
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sung Pil Hong MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Cheolju Lee PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hoguen Kim MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hoguen Kim MD, PhD.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 25 kb)

Supplementary material 2 (TIFF 37 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Song, M., Kim, H., Kim, W.K. et al. High Expression of AT-Rich Interactive Domain 3A (ARID3A) is Associated with Good Prognosis in Colorectal Carcinoma. Ann Surg Oncol 21 (Suppl 4), 481–489 (2014). https://doi.org/10.1245/s10434-013-3435-2

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-013-3435-2

Keywords

Search

Navigation