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Expression of phosphorylated Stat5 predicts expression of cyclin D1 and correlates with poor prognosis of colonic adenocarcinoma

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Purpose

Constitutive activation of signal transducer and activator of transcription-5 (Stat5) was recently found to be associated with tumor progression through stimulating cell proliferation and preventing apoptosis. However, it is not clear how activated Stat5 is expressed in colon cancer. We aimed to investigate the correlation between phosphorylated Stat5 (p-Stat5) expression and cell cycle regulators (cyclin D1) expression in colonic adenocarcinoma and the relationship between expression of these two proteins and various clinicopathological parameters, including overall survival.

Methods

P-Stat5 and cyclin D1 expression were determined by immunohistochemical staining from 169 cases of resected colonic adenocarcinoma specimens.

Results

P-Stat5 expression correlated with cyclin D1 expression (r = 0.250, P = 0.001). P-Stat5-positive staining was associated with the depth of tumor invasion (P = 0.002). Univariate survival analysis showed that lymph node metastasis, distant metastasis, TNM stage (all P < 0.0001), T stage (P = 0.024), p-Stat5-positive expression (P = 0.002), and cyclin D1-positive expression (P = 0.039) were associated with shorter survival in patients with colonic adenocarcinoma. Multivariate survival analysis showed that only distant metastasis (P < 0.001; hazard ratio [HR] = 4.96), TNM stage (P < 0.001; HR = 9.80), and p-Stat5 overexpression (P = 0.020; HR = 1.84) were independent predictors of poor prognosis.

Conclusions

Our findings provide the first evidence that p-Stat5 may play an important role in cyclin D1 overexpression and contribute to colonic adenocarcinoma progression.

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References

  1. Jemal A, Siegel R, Ward E et al (2009) Cancer statistics, 2009. CA Cancer J Clin 59:225–249

    Article  PubMed  Google Scholar 

  2. Toyoda Y, Nakayama T, Ito Y et al (2009) Trends in colorectal cancer incidence by subsite in Osaka, Japan. Jpn J Clin Oncol 39:189–191

    Article  PubMed  Google Scholar 

  3. Jung KW, Won YJ, Park S et al (2009) Cancer statistics in Korea: incidence, mortality and survival in 2005. J Korean Med Sci 24:995–1003

    Article  PubMed  Google Scholar 

  4. Bujanda L, Sarasqueta C, Hijona E et al (2010) Colorectal cancer prognosis twenty years later. World J Gastroenterol 16:862–867

    Article  PubMed  Google Scholar 

  5. De Roock W, Biesmans B, De Schutter J et al (2009) Clinical biomarkers in oncology: focus on colorectal cancer. Mol Diagn Ther 13:103–114

    PubMed  Google Scholar 

  6. Buettner R, Mora LB, Jove R (2002) Activated STAT signaling in human tumors provides novel molecular targets for therapeutic intervention. Clin Cancer Res 8:945–954

    CAS  PubMed  Google Scholar 

  7. Buitenhuis M, Coffer PJ, Koenderman L (2004) Signal transducer and activator of transcription 5 (STAT5). Int J Biochem Cell Biol 36:2120–2124

    Article  CAS  PubMed  Google Scholar 

  8. Nevalainen MT, Xie J, Torhorst J et al (2004) Signal transducer and activator of transcription-5 activation and breast cancer prognosis. J Clin Oncol 22:2053–2060

    Article  CAS  PubMed  Google Scholar 

  9. Lee TK, Man K, Poon RT et al (2006) Signal transducers and activators of transcription 5b activation enhances hepatocellular carcinoma aggressiveness through induction of epithelial–mesenchymal transition. Cancer Res 66:9948–9956

    Article  CAS  PubMed  Google Scholar 

  10. Xiong H, Su WY, Liang QC et al (2009) Inhibition of STAT5 induces G1 cell cycle arrest and reduces tumor cell invasion in human colorectal cancer cells. Lab Invest 89:717–725

    Article  CAS  PubMed  Google Scholar 

  11. Xiong H, Chen ZF, Liang QC et al (2009) Inhibition of DNA methyltransferase induces G2 cell cycle arrest and apoptosis in human colorectal cancer cells via inhibition of JAK2/STAT3/STAT5 signalling. J Cell Mol Med 13:3668–3679

    Article  PubMed  Google Scholar 

  12. Nam S, Williams A, Vultur A et al (2007) Dasatinib (BMS-354825) inhibits Stat5 signaling associated with apoptosis in chronic myelogenous leukemia cells. Mol Cancer Ther 6:1400–1405

    Article  CAS  PubMed  Google Scholar 

  13. Chien CM, Yang SH, Lin KL et al (2008) Novel indoloquinoline derivative, IQDMA, suppresses STAT5 phosphorylation and induces apoptosis in HL-60 cells. Chem Biol Interact 176:40–47

    Article  CAS  PubMed  Google Scholar 

  14. Liang QC, Xiong H, Zhao ZW et al (2009) Inhibition of transcription factor STAT5b suppresses proliferation, induces G1 cell cycle arrest and reduces tumor cell invasion in human glioblastoma multiforme cells. Cancer Lett 273:164–171

    Article  CAS  PubMed  Google Scholar 

  15. O’Connell JB, Maggard MA, Ko CY (2004) Colon cancer survival rates with the new American Joint Committee on Cancer sixth edition staging. J Natl Cancer Inst 96:1420–1425

    Article  PubMed  Google Scholar 

  16. Jass JR, Sobin LH, Watanabe H (1990) The World Health Organization’s histologic classification of gastrointestinal tumors. A commentary on the second edition. Cancer 66:2162–2167

    Article  CAS  PubMed  Google Scholar 

  17. Kusaba T, Nakayama T, Yamazumi K et al (2006) Activation of STAT3 is a marker of poor prognosis in human colorectal cancer. Oncol Rep 15:1445–1451

    CAS  PubMed  Google Scholar 

  18. Masuda M, Suzui M, Yasumatu R et al (2002) Constitutive activation of signal transducers and activators of transcription 3 correlates with cyclin D1 overexpression and may provide a novel prognostic marker in head and neck squamous cell carcinoma. Cancer Res 62:3351–3355

    CAS  PubMed  Google Scholar 

  19. Lewis RS, Ward AC (2008) Stat5 as a diagnostic marker for leukemia. Expert Rev Mol Diagn 8:73–82

    Article  CAS  PubMed  Google Scholar 

  20. Tan SH, Nevalainen MT (2008) Signal transducer and activator of transcription 5A/B in prostate and breast cancers. Endocr Relat Cancer 15:367–390

    Article  CAS  PubMed  Google Scholar 

  21. Li H, Ahonen TJ, Alanen K et al (2004) Activation of signal transducer and activator of transcription 5 in human prostate cancer is associated with high histological grade. Cancer Res 64:4774–4782

    Article  CAS  PubMed  Google Scholar 

  22. Li H, Zhang Y, Glass A et al (2005) Activation of signal transducer and activator of transcription-5 in prostate cancer predicts early recurrence. Clin Cancer Res 11:5863–5868

    Article  CAS  PubMed  Google Scholar 

  23. de Groot RP, Raaijmakers JA, Lammers JW et al (2000) STAT5-dependent cyclin D1 and Bcl-xL expression in Bcr-Abl-transformed cells. Mol Cell Biol Res Commun 3:299–305

    Article  PubMed  Google Scholar 

  24. Nevins JR (1992) E2F: a link between the Rb tumor suppressor protein and viral oncoproteins. Science 258:424–429

    Article  CAS  PubMed  Google Scholar 

  25. Huang WS, Wang JP, Wang T et al (2007) ShRNA-mediated gene silencing of beta-catenin inhibits growth of human colon cancer cells. World J Gastroenterol 13:6581–6587

    Article  CAS  PubMed  Google Scholar 

  26. Shan BE, Wang MX, Li RQ (2009) Quercetin inhibit human SW480 colon cancer growth in association with inhibition of cyclin D1 and survivin expression through Wnt/beta-catenin signaling pathway. Cancer Investig 27:604–612

    Article  CAS  Google Scholar 

  27. Itami A, Shimada Y, Watanabe G et al (1999) Prognostic value of p27(Kip1) and CyclinD1 expression in esophageal cancer. Oncology 57:311–317

    Article  CAS  PubMed  Google Scholar 

  28. Umekita Y, Ohi Y, Sagara Y et al (2002) Overexpression of cyclinD1 predicts for poor prognosis in estrogen receptor-negative breast cancer patients. Int J Cancer 98:415–418

    Article  CAS  PubMed  Google Scholar 

  29. Arici DS, Tuncer E, Ozer H et al (2009) Expression of retinoblastoma and cyclin D1 in gastric carcinoma. Neoplasma 56:63–67

    Article  CAS  PubMed  Google Scholar 

  30. Fu ZJ, Ma ZY, Wang QR et al (2008) Overexpression of CyclinD1 and underexpression of p16 correlate with lymph node metastases in laryngeal squamous cell carcinoma in Chinese patients. Clin Exp Metastasis 25:887–892

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This study was supported by a grant from the Natural Science Fund of Heilongjiang Province (key projects; no. ZD 200804-02) and the Science Technological Research Funds of the Department of Education of Heilongjiang Province (no. 11551295 and no. 11541224).

Conflicts of interest statement

No conflicts of interest exist in the submission of this manuscript.

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Authors and Affiliations

  1. Department of Gastrointestinal Medical Oncology, The Affiliated Tumor Hospital of Harbin Medical University, No. 150, Haping Road, Harbin, Heilongjiang Province, 150040, China

    Yinling Mao, Zhiwei Li & Changjie Lou

  2. Department of Gastrointestinal Medical Oncology, The Affiliated Tumor Hospital of Harbin Medical University, Institute of treatment and prevention of tumour of Heilongjiang Province, No. 150, Haping Road, Harbin, Heilongjiang Province, 150040, China

    Yanqiao Zhang

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  1. Yinling Mao
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  2. Zhiwei Li
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  4. Yanqiao Zhang
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Correspondence to Yanqiao Zhang.

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Mao, Y., Li, Z., Lou, C. et al. Expression of phosphorylated Stat5 predicts expression of cyclin D1 and correlates with poor prognosis of colonic adenocarcinoma. Int J Colorectal Dis 26, 29–35 (2011). https://doi.org/10.1007/s00384-010-1090-7

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  • DOI: https://doi.org/10.1007/s00384-010-1090-7

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