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Clinical significance of RKIP mRNA expression in non-small cell lung cancer

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Tumor Biology

Abstract

Raf-1 kinase inhibitor protein (RKIP) expression was associated with the onset, development, invasion, and metastasis of numerous tumor types including prostate cancer, melanoma, colorectal cancer, liver cancer, and breast cancer. However, RKIP mRNA expression and the clinical significance in non-small cell lung cancers (NSCLC) remain unresolved. Real-time PCR was performed to detect the expression of RKIP mRNA in 126 pairs of lung tumor tissues (TT) and surrounding normal tissues (sNT). Correlations between RKIP mRNA expression and clinicopathological features were evaluated by statistical analysis. In the 126 patients examined, RKIP mRNA expression was significantly lower in lung TT than the sNT (p < 0.05). Our results indicated that downregulation of RKIP mRNA expression was associated with a poorer N-stage (p = 0.019) and poorer pathological TNM stage (p = 0.015). However, no significant association was observed between the expression status of RKIP mRNA and clinicopathologic factors, such as gender, age, histological type, and the size of the tumor (p > 0.05). The level of RKIP mRNA expression was found to be significantly downregulated in NSCLC, and the lower mRNA levels correlated with poorer differentiation, advanced pathologic TNM stage in patients with NSCLC.

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References

  1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63(1):11–30.

    Article  PubMed  Google Scholar 

  2. Molina JR, Yang P, Cassivi SD, Schild SE, Adjei AA. Non-small cell lung cancer: epidemiology, risk factors, treatment, and survivorship. Mayo Clin Proc. 2008;83:584–94.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Alberg AJ, Brock MV, Ford JG, Samet JM, Spivack SD. Epidemiology of lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143(5 Suppl):e1S–e29S.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in Oncology: Non-Small Cell Lung Cancer, Version 2, 2013. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp#nscl

  5. Yeung K, Janosch P, McFerran B, Rose DW, Mischak H, et al. Mechanism of suppression of the Raf/MEK/extracellular signal-regulated kinase pathway by the raf kinase inhibitor protein. Mol Cell Biol. 2000;20:3079–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Granovsky AE, Rosner MR. Raf kinase inhibitory protein: a signal transduction modulator and metastasis suppressor. Cell Res. 2008;18(4):452–7.

    Article  CAS  PubMed  Google Scholar 

  7. Beshir AB, Ren G, Magpusao AN, Barone LM, Yeung KC, Fenteany G. Raf kinase inhibitor protein suppresses nuclear factor-κB-dependent cancer cell invasion through negative regulation of matrix metalloproteinase expression. Cancer Lett. 2010;299(2):137–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Zeng L, Imamoto A, Rosner MR. Raf kinase inhibitory protein (RKIP): a physiological regulator and future therapeutic target. Expert Opin Ther Targets. 2008;12(10):1275–87. doi:10.1517/14728222.12.10.1275.

    Article  CAS  PubMed  Google Scholar 

  9. Fu Z, Smith PC, Zhang L, Rubin MA, Dunn RL, Yao Z, et al. Effects of Raf kinase inhibitor protein expression on suppression of prostate cancer metastasis. J Natl Cancer Inst. 2003;95(12):878–89.

    Article  CAS  PubMed  Google Scholar 

  10. Xu YF, Yi Y, Qiu SJ, Gao Q, Li YW, Dai CX, et al. PEBP1 downregulation is associated to poor prognosis in HCC related to hepatitis B infection. J Hepatol. 2010;53(5):872–9.

    Article  CAS  PubMed  Google Scholar 

  11. Lin K, Baritaki S, Militello L, Malaponte G, Bevelacqua Y, Bonavida B. The role of B-RAF mutations in melanoma and the induction of EMT via dysregulation of the NF-kappaB/Snail/RKIP/PTEN circuit. Genes Cancer. 2010;1(5):409–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Al-Mulla F, Hagan S, Al-Ali W, Jacob SP, Behbehani AI, Bitar MS, et al. Raf kinase inhibitor protein: mechanism of loss of expression and association with genomic instability. J Clin Pathol. 2008;61(4):524–9.

    Article  CAS  PubMed  Google Scholar 

  13. Li HZ, Gao Y, Zhao XL, Liu YX, Sun BC, Yang J, et al. Effects of Raf kinase inhibitor protein expression on metastasis and progression of human breast cancer. Mol Cancer Res. 2009;7(6):832–40.

    Article  CAS  PubMed  Google Scholar 

  14. Beach S, Tang H, Park S, Dhillon AS, Keller ET, Kolch W, et al. Snail is a repressor of RKIP transcription in metastatic prostate cancer cells. Oncogene. 2008;27(15):2243–8.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by a grant form Nanjing General Hospital Foundation “Cancer associated fibroblasts promote angiogenesis and metastasis by secreting periostin in non-small cell lung cancer” (2013020).

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Correspondence to Yi Shi.

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Wang, Q., Wu, X., Wu, T. et al. Clinical significance of RKIP mRNA expression in non-small cell lung cancer. Tumor Biol. 35, 4377–4380 (2014). https://doi.org/10.1007/s13277-013-1575-4

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  • DOI: https://doi.org/10.1007/s13277-013-1575-4

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