Asian Pacific Journal of Cancer Prevention

  • 제14권6호
  • /
  • Pages.3725-3728
  • /
  • 2013
  • /
  • 1513-7368(pISSN)
  • /
  • 2476-762X(eISSN)
아시아태평양암예방학회 (Asian Pacific Journal of Cancer Prevention)
권호 표지
DOI QR코드

DOI QR Code

Prognostic Value of Phosphorylated mTOR/RPS6KB1 in Non-small Cell Lung Cancer

  • Zhang, Yong (Department of Respiratory Medicine, West China Hospital of Sichuan University) ;
  • Ni, Huan-Juan (Department of Emergency, Affiliated Hospital of Panzhihua University) ;
  • Cheng, De-Yun (Department of Respiratory Medicine, West China Hospital of Sichuan University)
  • 발행 : 2013.06.30
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Background: The mammalian target of rapamycin (mTOR) /RPS6KB1 activation has recently been implicated in tumour development, but its role in lung cancer remains unclear. The aim of this study was to explore the role of mTOR/RPS6KB1 signaling pathway in non-small-cell lung cancer (NSCLC). Methods: Immunohistochemistry was performed to assess the expression of phosphorylated mammalian target of rapamycin (p-mTOR) and its downstream ribosomal phosphorylated RPS6KB1 (p-RPS6KB1) in NSCLC patients. We also analyzed p-mTOR/p-RPS6KB1 protein expression in 45 fresh NSCLC tissues using Western blotting. Results: The expression level of p-mTOR and p-RPS6KB1 was significantly higher in NSCLC tumor specimens than that in adjacent noncancerous normal lung tissues (P<0.01). p-mTOR expression correlated with p-RPS6KB1. Furthermore, high expression level of p-mTOR or p-RPS6KB1 in NSCLC was associated with a shorter overall survival (both P<0.01). Multivariate analysis indicated high level of p-mTOR expression was an independent prognostic factor (HR=2.642, 95%CI 1.157-4.904, p=0.002). Conclusions: p-mTOR and p-RPS6KB1 could be useful prognostic markers for NSCLC.

키워드

참고문헌

  1. Baxi SM, Tan W, Murphy ST, Smeal T, Yin MJ (2012). Targeting 3-phosphoinoside -dependent kinase-1 to inhibit insulin-like growth factor-I induced AKT and p70 S6 kinase activation in breast cancer cells. PLoS One, 7, e48402. https://doi.org/10.1371/journal.pone.0048402
  2. Chen J, Fang Y (2002). A novel pathway regulating the mammalian target of rapamycin (mTOR) signaling. Biochem Pharmacol, 64, 1071-7. https://doi.org/10.1016/S0006-2952(02)01263-7
  3. Dong QZ, Wang Y, Dong XJ, et al (2011). CIP2A is overexpressed in non-small cell lung cancer and correlates with poor prognosis. Ann Surg Oncol, 218, 857-65.
  4. Ferrara N, Gerber HP, LeCouter J (2003). The biology of VEGF and its receptors. Nat Med, 9, 669-76. https://doi.org/10.1038/nm0603-669
  5. Friday BB, Adjei AA (2005). K-ras as a target for cancer therapy. Biochim Biophys Acta, 1756, 127-44.
  6. Huang S, Houghton PJ (2003). Targeting mTOR signaling for cancer therapy. Curr Opin Pharmacol, 3, 371-7. https://doi.org/10.1016/S1471-4892(03)00071-7
  7. Ip CK, Wong AS (2012). Exploiting p70 S6 kinase as a target for ovarian cancer. Expert Opin Ther Targets, 16, 619-30. https://doi.org/10.1517/14728222.2012.684680
  8. Jemal A, Siegel R, Xu J, Ward E (2010). Cancer statistics, 2010. CA Cancer J Clin, 60, 277-300. https://doi.org/10.3322/caac.20073
  9. Ma XM, Blenis J (2009). Molecular mechanisms of mTORmediated translational control. Nat Rev Mol Cell Biol, 10, 307-18. https://doi.org/10.1038/nrm2672
  10. Malik PS, Sharma MC, Mohanti BK, et al (2013). Clinicopathological Profile of Lung Cancer at AIIMS: A Changing Paradigm in India. Asian Pac J Cancer Prev, 14, 489-94. https://doi.org/10.7314/APJCP.2013.14.1.489
  11. Matsubara H, Sakakibara K, Kunimitsu T, et al (2012). Nonsmall cell lung carcinoma therapy using mTOR-siRNA. Int J Clin Exp Pathol, 5, 119-25.
  12. Menon S, Manning BD (2008). Common corruption of the mTOR signaling network in human tumors. Oncogene, 27, S43-51. https://doi.org/10.1038/onc.2009.352
  13. Minna JD, Roth JA, Gazdar AF (2002). Focus on lung cancer. Cancer Cell, 1, 49-52. https://doi.org/10.1016/S1535-6108(02)00027-2
  14. Shaw RJ, Cantley LC (2006). Ras, PI(3)K and mTOR signalling controls tumour cell growth. Nature, 441, 424-30. https://doi.org/10.1038/nature04869
  15. Thomas A, Rajan A, Lopez-Chavez A, Wang Y, Giaccone G (2013). From targets to targeted therapies and molecular profiling in non-small cell lung carcinoma. Ann Oncol, 24, 577-85. https://doi.org/10.1093/annonc/mds478
  16. Tsurutani J, Fukuoka J, Tsurutani H, et al (2006). Evaluation of two phosphorylation sites improves the prognostic significance of Akt activation in non-small-cell lung cancer tumors. J Clin Oncol, 24, 306-14.
  17. Wang D, Chen J, Guo F, et al (2011). Clinical significance of p-mTOR and p-mTOR protein expression in human colorectal carcinomas. Asian Pac J Cancer Prev, 12, 2581-4.
  18. Zhao XF, Zhao MY, Chai L, et al (2013). Amplified RPS6KB1 and CDC2 genes are potential biomarkers for aggressive HIV+/EBV+ diffuse large B-cell lymphomas. Int J Clin Exp Pathol, 6, 148-54.

피인용 문헌

  1. The Prognostic Role of mTOR and P-mTOR for Survival in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis vol.10, pp.2, 2015, https://doi.org/10.1371/journal.pone.0116771
  2. Expression and clinical significance of mammalian target of rapamycin/P70 ribosomal protein S6 kinase signaling pathway in human colorectal carcinoma tissue pp.1792-1082, 2015, https://doi.org/10.3892/ol.2015.3228
  3. The p70S6K Specific Inhibitor PF-4708671 Impedes Non-Small Cell Lung Cancer Growth vol.11, pp.1, 2016, https://doi.org/10.1371/journal.pone.0147185