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Expression and prognostic significance of GATA-binding protein 2 in colorectal cancer

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Abstract

GATA-binding protein 2 (GATA2) is a nuclear transcription factor that plays a critical role in tumorigenesis. High levels of GATA2 expression are correlated with poor survival outcomes in many types of cancer. However, the expression and prognostic significance of GATA2 in colorectal cancer remain unknown. In this study, GATA2 protein expression was examined using immunohistochemistry in 307 colorectal cancer tissues, and its association with clinicopathological features and prognosis was analyzed. The expression of GATA2 was found to be significantly higher in colorectal cancer tissues than in matched adjacent noncancerous tissues (60.3 vs. 9.0 %, P < 0.0001). The expression of GATA2 was significantly correlated with tumor location (P = 0.005), histological type (P = 0.019), and recurrence (P = 0.009). Kaplan–Meier survival analysis demonstrated that patients with high levels of GATA2 expression had worse disease-free survival outcomes than those with low levels of GATA2 expression (P = 0.016). Univariate analysis showed high levels of GATA2 expression to be significantly associated with shorter periods of disease-free survival (HR 2.196; 95 % CI 1.142–4.226; P = 0.018). Multivariate analysis showed GATA2 expression to be an independent prognostic factor for patients with colorectal cancer (HR 1.952; 95 % CI 1.010–3.775; P = 0.047). These findings suggest that high levels of GATA2 expression may be a useful indicator of disease recurrence after curative colorectal cancer treatment.

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References

  1. Qaseem A, Denberg TD, Hopkins RH Jr, Humphrey LL, Levine J, Sweet DE, Shekelle P, Clinical Guidelines Committee of the American College of Physicians. Screening for colorectal cancer: a guidance statement from the American College of Physicians. Ann Intern Med. 2012;156:378–86.

    Article  PubMed  Google Scholar 

  2. Cunningham D, Atkin W, Lenz HJ, Lynch HT, Minsky B, Nordlinger B, Starling N. Colorectal cancer. Lancet. 2010;375:1030–47.

    Article  PubMed  Google Scholar 

  3. Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin. 2011;61:212–36.

    Article  PubMed  Google Scholar 

  4. Grady WM, Carethers JM. Genomic and epigenetic instability in colorectal cancer pathogenesis. Gastroenterology. 2008;135:1079–99.

    Article  PubMed  CAS  Google Scholar 

  5. Evans T, Reitman M, Felsenfeld G. An erythrocyte-specific DNA-binding factor recognizes a regulatory sequence common to all chicken globin genes. Proc Natl Acad Sci USA. 1988;85:5976–80.

    Article  PubMed  CAS  Google Scholar 

  6. Tsai SF, Martin DI, Zon LI, D’Andrea AD, Wong GG, Orkin SH. Cloning of cDNA for the major DNA-binding protein of the erythroid lineage through expression in mammalian cells. Nature. 1989;339:446–51.

    Article  PubMed  CAS  Google Scholar 

  7. Gilliland DG. Hematologic malignancies. Curr Opin Hematol. 2001;8:189–91.

    Article  PubMed  CAS  Google Scholar 

  8. Zhang SJ, Ma LY, Huang QH, Li G, Gu BW, Gao XD, Shi JY, Wang YY, Gao L, Cai X, Ren RB, Zhu J, Chen Z, Chen SJ. Gain-of-function mutation of GATA-2 in acute myeloid transformation of chronic myeloid leukemia. Proc Natl Acad Sci USA. 2008;105:2076–81.

    Article  PubMed  CAS  Google Scholar 

  9. Luesink M, Hollink IH, van der Velden VH, Knops RH, Boezeman JB, de Haas V, Trka J, Baruchel A, Reinhardt D, van der Reijden BA, van den Heuvel-Eibrink MM, Zwaan CM, Jansen JH. High GATA2 expression is a poor prognostic marker in pediatric acute myeloid leukemia. Blood. 2012;120:2064–75.

    Article  PubMed  CAS  Google Scholar 

  10. Kazenwadel J, Secker GA, Liu YJ, Rosenfeld JA, Wildin RS, Cuellar-Rodriguez J, Hsu AP, Dyack S, Fernandez CV, Chong CE, Babic M, Bardy PG, Shimamura A, Zhang MY, Walsh T, Holland SM, Hickstein DD, Horwitz MS, Hahn CN, Scott HS, Harvey NL. Loss-of-function germline GATA2 mutations in patients with MDS/AML or MonoMAC syndrome and primary lymphedema reveal a key role for GATA2 in the lymphatic vasculature. Blood. 2012;119:1283–91.

    Article  PubMed  CAS  Google Scholar 

  11. Vicente C, Conchillo A, García-Sánchez MA, Odero MD. The role of the GATA2 transcription factor in normal and malignant hematopoiesis. Crit Rev Oncol Hematol. 2012;82:1–17.

    Article  PubMed  Google Scholar 

  12. Wang Y, He X, Ngeow J, Eng C. GATA2 negatively regulates PTEN by preventing nuclear translocation of androgen receptor and by androgen-independent suppression of PTEN transcription in breast cancer. Hum Mol Genet. 2012;21:569–76.

    Article  PubMed  CAS  Google Scholar 

  13. Böhm M, Locke WJ, Sutherland RL, Kench JG, Henshall SM. A role for GATA-2 in transition to an aggressive phenotype in prostate cancer through modulation of key androgen-regulated genes. Oncogene. 2009;28:3847–56.

    Article  PubMed  Google Scholar 

  14. Kumar MS, Hancock DC, Molina-Arcas M, Steckel M, East P, Diefenbacher M, Armenteros-Monterroso E, Lassailly F, Matthews N, Nye E, Stamp G, Behrens A, Downward J. The GATA2 transcriptional network is requisite for RAS oncogene-driven non-small cell lung cancer. Cell. 2012;149:642–55.

    Article  PubMed  CAS  Google Scholar 

  15. Steckel M, Molina-Arcas M, Weigelt B, Marani M, Warne PH, Kuznetsov H, Kelly G, Saunders B, Howell M, Downward J, Hancock DC. Determination of synthetic lethal interactions in KRAS oncogene-dependent cancer cells reveals novel therapeutic targeting strategies. Cell Res. 2012;22:1227–45.

    Article  PubMed  CAS  Google Scholar 

  16. Xing X, Peng L, Qu L, Ren T, Dong B, Su X, Shou C. Prognostic value of PRL-3 overexpression in early stages of colonic cancer. Histopathology. 2009;54:309–18.

    Article  PubMed  Google Scholar 

  17. Wall L, deBoer E, Grosveld F. The human beta-globin gene 3′ enhancer contains multiple binding sites for an erythroid-specific protein. Genes Dev. 1988;2:1089–100.

    Article  PubMed  CAS  Google Scholar 

  18. Tsai FY, Keller G, Kuo FC, Weiss M, Chen J, Rosenblatt M, Alt FW, Orkin SH. An early haematopoietic defect in mice lacking the transcription factor GATA-2. Nature. 1994 15;371:221–6.

    Google Scholar 

  19. Allegra CJ, Jessup JM, Somerfield MR, Hamilton SR, Hammond EH, Hayes DF, McAllister PK, Morton RF, Schilsky RL. American Society of Clinical Oncology provisional clinical opinion: testing for KRAS gene mutations in patients with metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor monoclonal antibody therapy. J Clin Oncol. 2009;27:2091–6.

    Article  PubMed  Google Scholar 

  20. Bardelli A, Jänne PA. The road to resistance: EGFR mutation and cetuximab. Nat Med. 2012;18:199–200.

    Article  PubMed  CAS  Google Scholar 

  21. Karapetis CS, Khambata-Ford S, Jonker DJ, O’Callaghan CJ, Tu D, Tebbutt NC, Simes RJ, Chalchal H, Shapiro JD, Robitaille S, Price TJ, Shepherd L, Au HJ, Langer C, Moore MJ, Zalcberg JR. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med. 2008;359:1757–65.

    Article  PubMed  CAS  Google Scholar 

  22. Shibayama M, Maak M, Nitsche U, Gotoh K, Rosenberg R, Janssen KP. Prediction of metastasis and recurrence in colorectal cancer based on gene expression analysis: ready for the clinic? Cancers. 2011;3:2858–69.

    Article  Google Scholar 

  23. Yu X, McBean AM. Screening mammography use and chemotherapy among female stage II colon cancer patients: a retrospective cohort study. BMC Health Serv Res. 2010;10:98.

    Article  PubMed  Google Scholar 

  24. Storli KE, Søndenaa K, Bukholm IR, Nesvik I, Bru T, Furnes B, Hjelmeland B, Iversen KB, Eide GE. Overall survival after resection for colon cancer in a national cohort study was adversely affected by TNM stage, lymph node ratio, gender, and old age. Int J Colorectal Dis. 2011;26:1299–307.

    Article  PubMed  Google Scholar 

  25. Kune GA, Kune S, Field B, White R, Brough W, Schellenberger R, Watson LF. Survival in patients with large-bowel cancer. A population-based investigation from the Melbourne Colorectal Cancer Study. Dis Colon Rectum. 1990;33:938–46.

    Article  PubMed  CAS  Google Scholar 

  26. Enblad P, Adami HO, Bergström R, Glimelius B, Krusemo U, Påhlman L. Improved survival of patients with cancers of the colon and rectum? J Natl Cancer Inst. 1988;80:586–91.

    Article  PubMed  CAS  Google Scholar 

  27. Petrek JA, Sandberg WA, Bean PK. The role of gender and other factors in the prognosis of young patients with colorectal cancer. Cancer. 1985;56:952–5.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We thank Dr. Bin Dong and Dr. Zhongwu Li for histopathological diagnosis. We thank Dr. Like Qu for the valuable suggestions. This study was supported by the grants from the National Natural Science Foundation of China (No. 81272766 and No. 81071658), Capital Medical Development and Research Foundation (No. 2009–2093), Clinical Characteristics and Application Research of Capital (No. Z121107001012130), Beijing Natural Science Foundation (No. 7132054), New Star of Science and Technology Program of Beijing (No. 2011060), National 863 Program (No. 2007AA021103).

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Minimally Invasive Gastrointestinal Surgery, Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing, 100142, China

    Lei Chen, Beihai Jiang, Zaozao Wang, Maoxing Liu, Yiyuan Ma, Hong Yang, Jiadi Xing, Chenghai Zhang, Zhendan Yao, Nan Zhang, Ming Cui & Xiangqian Su

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  1. Lei Chen
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  2. Beihai Jiang
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  3. Zaozao Wang
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Correspondence to Xiangqian Su.

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Lei Chen and Beihai Jiang contributed equally to this work.

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Chen, L., Jiang, B., Wang, Z. et al. Expression and prognostic significance of GATA-binding protein 2 in colorectal cancer. Med Oncol 30, 498 (2013). https://doi.org/10.1007/s12032-013-0498-7

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