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The prognostic value of Smad4 mRNA in patients with prostate cancer

  • Research Article
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Tumor Biology

Abstract

The tumor suppressor gene Smad4 has been localized to chromosome 18q21.1 and is a member of the Smad family that mediates the transforming growth factor β signaling pathway suppressing epithelial cell growth. However, variable expression of Smad4 messenger RNA (mRNA) has been reported, with a loss in some cancers and increased expression in others. The aim of the present study was to investigate the Smad4 mRNA expression in prostate cancer tissues and adjacent noncancerous tissues and its potential relevance to clinicopathological variables and prognosis. The expression change of Smad4 mRNA was detected by using real-time quantitative reverse transcriptase-polymerase chain reaction analysis. The data showed that the Smad4 mRNA expression level in prostate cancer tissues was significantly lower than those in noncancerous tissues. The results indicated that the low expression of Smad4 mRNA in prostate cancer was associated with lymph node metastasis, preoperative prostate-specific antigen (PSA), and Gleason score. Kaplan–Meier survival analysis showed that patients with high Smad4 mRNA expression have longer biochemical recurrence-free survival time compared to patients with low Smad4 mRNA expression. Multivariate analysis revealed that Smad4 mRNA expression was an independent predictor of biochemical recurrence-free survival. Our results emphasize that Smad4 mRNA can be used as a predictive biomarker.

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References

  1. Siegel R, Ward E, Brawley O, Jemal A. Cancer statistics, 2011. CA Cancer J Clin. 2011;61:212–36.

    Article  PubMed  Google Scholar 

  2. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60:277–300.

    Article  PubMed  Google Scholar 

  3. Zhang H, Qi C, Li L, Luo F, Xu Y. Clinical significance of NUCB2 mRNA expression in prostate cancer. J Exp Clin Cancer Res. 2013;32:56.

    Article  PubMed Central  PubMed  Google Scholar 

  4. Zhang H, Qi C, Wang A, Li L, Xu Y. High expression of nucleobindin 2 mRNA: an independent prognostic factor for overall survival of patients with prostate cancer. Tumor Biol. 2013. doi:10.1007/s13277-013-1268-z.

  5. Zhang H, Qi C, Wang A, Yao B, Li L, Wang Y, et al. Prognostication of prostate cancer based on NUCB2 protein assessment: NUCB2 in prostate cancer. J Exp Clin Cancer Res. 2013;32:77.

    Article  PubMed Central  PubMed  Google Scholar 

  6. Attisano L, Wrana JL. Signal transduction by the TGF-β superfamily. Science. 2002;296:1646–7.

    Article  CAS  PubMed  Google Scholar 

  7. Attisano L, Tuen L-HS. The Smads. Genome Biol. 2001;2:3010.1–8.

    Article  Google Scholar 

  8. Shi Y, Massague J. Mechanisms of TGF-β signaling from cell membrane to the nucleus. Cell. 2003;13:685–700.

    Article  Google Scholar 

  9. Itoh S, Itoh F, Goumans MJ, Ten Dijke P. Signaling of transforming growth factor-beta family members through Smad proteins. Eur J Biochem. 2000;267:6954–67.

    Article  CAS  PubMed  Google Scholar 

  10. Ten Dijke P, Goumans MJ, Itoh F, Itoh S. Regulation of cell proliferation by Smad proteins. J Cell Physiol. 2002;191:1–16.

    Article  PubMed  Google Scholar 

  11. MacGrogan D, Pegram M, Slamon D, Bookstein R. Comparative mutational analysis of DPC4 (Smad4) in prostatic and colorectal carcinomas. Oncogene. 1997;15:1111–4.

    Article  CAS  PubMed  Google Scholar 

  12. Yang L, You S, Kumar V, Zhang C, Cao Y. In vitro the behaviors of metastasis with suppression of VEGF in human bone metastatic LNCaP-derivative C4-2B prostate cancer cell line. J Exp Clin Cancer Res. 2012;31:40.

    Article  PubMed Central  PubMed  Google Scholar 

  13. Ribeiro R, Monteiro C, Cunha V, Oliveira MJ, Freitas M, Fraga A, et al. Human periprostatic adipose tissue promotes prostate cancer aggressiveness in vitro. J Exp Clin Cancer Res. 2012;31:32.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  14. Zhou Y, Su Z, Huang Y, Sun T, Chen S, Wu T, et al. The Zfx gene is expressed in human gliomas and is important in the proliferation and apoptosis of the human malignant glioma cell line U251. J Exp Clin Cancer Res. 2011;30:114.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Li Z, Tanaka H, Galiano F, Glass J. Anticancer activity of the iron facilitator LS081. J Exp Clin Cancer Res. 2011;30:34.

    Article  PubMed Central  PubMed  Google Scholar 

  16. Kanamori M, Sano A, Yasuda T, Hori T, Suzuki K. Array-based comparative genomic hybridization for genomic-wide screening of DNA copy number alterations in aggressive bone tumors. J Exp Clin Cancer Res. 2012;31:100.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Piscitelli P, Barba M, Crespi M, Di Maio M, Santoriello A, D’Aiuto M, et al. The burden of breast cancer in Italy: mastectomies and quadrantectomies performed between 2001 and 2008 based on nationwide hospital discharge records. J Exp Clin Cancer Res. 2012;31:96.

    Article  PubMed Central  PubMed  Google Scholar 

  18. Zhang H, Li L, Xu Y. CYP1B1 polymorphisms and susceptibility to prostate cancer: a meta-analysis. PLoS One. 2013;8:e68634.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Zhang H, Xu Y, Zhang Z, Liu R, Ma B. Association between COX-2 rs2745557 polymorphism and prostate cancer risk: a systematic review and meta-analysis. BMC Immunol. 2012;13:14.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Zhang H, Ma H, Xu Y, Li L. Association of SMAD7 rs12953717 polymorphism with cancer: a meta-analysis. PLoS ONE. 2013;8:e58170.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Zhang H, Ma H, Li L, Zhang Z, Xu Y. Association of methylenetetrahydrofolate dehydrogenase 1 polymorphisms with cancer: a meta-analysis. PLoS One. 2013;8:e69366.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Maio M, Ascierto P, Testori A, Ridolfi R, Bajetta E, Queirolo P, et al. The cost of unresectable stage III or stage IV melanoma in Italy. J Exp Clin Cancer Res. 2012;31:91.

    Article  PubMed Central  PubMed  Google Scholar 

  23. Solivetti FM, Elia F, Graceffa D, Di Carlo A. Ultrasound morphology of inguinal lymph nodes may not herald an associated pathology. J Exp Clin Cancer Res. 2012;31:88.

    Article  PubMed Central  PubMed  Google Scholar 

  24. Ozasa R, Ohno J, Iwahashi T, Taniguchi K. Tumor-induced lymphangiogenesis in cervical lymph nodes in oral melanoma-bearing mice. J Exp Clin Cancer Res. 2012;31:83.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Bartolo M, Zucchella C, Pace A, De Nunzio AM, Serrao M, Sandrini G, et al. Improving neuro-oncological patients care: basic and practical concepts for nurse specialist in neuro-rehabilitation. J Exp Clin Cancer Res. 2012;31:82.

    Article  PubMed Central  PubMed  Google Scholar 

  26. Cuozzo F, Raciti M, Bertelli L, Parente R, Di Renzo L. Pro-death and pro-survival properties of ouabain in U937 lymphoma derived cells. J Exp Clin Cancer Res. 2012;31:95.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  27. Hsu CM, Lin PM, Wang YM, Chen ZJ, Lin SF, Yang MY. Circulating miRNA is a novel marker for head and neck squamous cell carcinoma. Tumor Biol. 2012;33(6):1933–42.

    Article  CAS  Google Scholar 

  28. Pandith AA, Siddiqi MA. Burden of cancers in the valley of Kashmir: 5 year epidemiological study reveals a different scenario. Tumor Biol. 2012;33(5):1629–37.

    Article  Google Scholar 

  29. Ma Y, Liang D, Liu J, Axcrona K, Kvalheim G, Giercksky KE, et al. Synergistic effect of SCF and G-CSF on stem-like properties in prostate cancer cell lines. Tumor Biol. 2012;33(4):967–78.

    Article  CAS  Google Scholar 

  30. Pinto A, Merino M, Zamora P, Redondo A, Castelo B, Espinosa E. Targeting the endothelin axis in prostate carcinoma. Tumor Biol. 2012;33(2):421–6.

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Urology, First Affiliated Hospital of Liaoning Medical University, Jinzhou, 121001, China

    Da-Tian Zhang, Jian-Guo Shi, Yian Liu & Hua-Mao Jiang

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  1. Da-Tian Zhang
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  2. Jian-Guo Shi
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  3. Yian Liu
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  4. Hua-Mao Jiang
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Correspondence to Hua-Mao Jiang.

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Zhang, DT., Shi, JG., Liu, Y. et al. The prognostic value of Smad4 mRNA in patients with prostate cancer. Tumor Biol. 35, 3333–3337 (2014). https://doi.org/10.1007/s13277-013-1439-y

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  • DOI: https://doi.org/10.1007/s13277-013-1439-y

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