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Prognostic Significance of 14-3-3γ Overexpression in Advanced Non-Small Cell Lung Cancer

  • Published : 2014.04.30

Abstract

The 14-3-3 protein has been shown to be involved in the cancer process. However, there is no understanding of the relationship between 14-3-$3{\gamma}$ (14-3-3 gamma) expression and prognosis in advanced non-small cell lung cancer. In this study, we therefore investigated the association between protein levels by immunohistochemistry and clinicopathological features of advanced NSCLC patients. Survival curves were estimated using the Kaplan-Meier method and tested by log-rank. Multivariate analysis was conducted with the Cox's regression model to determine independence of factors. p values less than 0.05 were considered significant. A total 153 patients were studied, with 54.3% being stage III and 45.8% stage IV. Fifty-one cases (33.3%) were squamous cell carcinomas, and 98 cases (64.1%) were adenocarcinomas. High 14-3-$3{\gamma}$ expression was seen in 59.5% and significantly correlated with lymph node metastasis (p=0.010) and distant metastasis (p=0.017). On Kaplan-Meier analysis, high 14-3-$3{\gamma}$ expression was associated with poorer survival with a marginal trend toward significance (p=0.055). On multivariate analysis, age, treatment, and 14-3-$3{\gamma}$ expression proved to be independent prognostic parameters. In vitro experiments indicated that 14-3-$3{\gamma}$ overexpression also played a potential role in cancer invasion. In conclusion, our data suggest that 14-3-$3{\gamma}$ overexpression is associated with invasion and a poor prognosis. Therefore, 14-3-$3{\gamma}$ may be a potential prognostic marker of advanced non-small cell lung cancer.

References

  1. Aitken A (2006). 14-3-3 proteins: a historic overview. Semin Cancer Biol, 16, 162-72. https://doi.org/10.1016/j.semcancer.2006.03.005
  2. Ajjappala BS, Kim YS, Kim MS, et al (2009). 14-3-3gamma is stimulated by IL-3 and promotes cell proliferation. J Immunol, 182, 1050-60. https://doi.org/10.4049/jimmunol.182.2.1050
  3. Fu H, Subramanian RR, Masters SC (2000). 14-3-3 proteins:structure, function, and regulation. Annu Rev Pharmacol Toxicol, 40, 617-47. https://doi.org/10.1146/annurev.pharmtox.40.1.617
  4. Herbst RS, Heymach JV, Lippman SM (2008). Lung cancer. N Engl J Med, 359, 1367-80. https://doi.org/10.1056/NEJMra0802714
  5. Hermeking H (2003). The 14-3-3 cancer connection. Nat Rev Cancer, 3, 931-43. https://doi.org/10.1038/nrc1230
  6. Horie M, Suzuki M, Takahashi E, et al (1999). Cloning, expression, and chromosomal mapping of the human 14-3-3gamma gene (YWHAG) to 7q11.23. Genomics, 60, 241-3. https://doi.org/10.1006/geno.1999.5887
  7. Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90. https://doi.org/10.3322/caac.20107
  8. Jin YH, Kim YJ, Kim DW, et al (2008). Sirt2 interacts with 14-3-3 beta/gamma and down-regulates the activity of p53. Biochem Biophys Res Commun, 368, 690-5. https://doi.org/10.1016/j.bbrc.2008.01.114
  9. Ko BS, Lai IR, Chang TC, et al (2011). Involvement of 14-3-3gamma overexpression in extrahepatic metastasis of hepatocellular carcinoma. Hum Pathol, 42, 129-35. https://doi.org/10.1016/j.humpath.2010.01.028
  10. Lirdprapamongkol K, Kramb JP, Suthiphongchai T, et al (2009). Vanillin suppresses metastatic potential of human cancer cells through PI3K inhibition and decreases angiogenesis in vivo. J Agric Food Chem, 57, 3055-63. https://doi.org/10.1021/jf803366f
  11. Morrison DK (2009). The 14-3-3 proteins: integrators of diverse signaling cues that impact cell fate and cancer development. Trends Cell Biol, 19, 16-23. https://doi.org/10.1016/j.tcb.2008.10.003
  12. Peng CY, Graves PR, Thoma RS, et al (1997). Mitotic and G2 checkpoint control: regulation of 14-3-3 protein binding by phosphorylation of Cdc25C on serine-216. Science, 277, 1501-05. https://doi.org/10.1126/science.277.5331.1501
  13. Qi W, Liu X, Chen W, et al (2003). Overexpression of 14-3-3gamma causes polyploidization in H322 lung cancer cells. Mol Carcinog, 46, 847-56.
  14. Qi W, Liu X, Qiao D, et al (2005). Isoform-specific expression of 14-3-3 proteins in human lung cancer tissues. Int J Cancer, 113, 359-63. https://doi.org/10.1002/ijc.20492
  15. Radhakrishnan VM, Martinez JD (2010). 14-3-3gamma induces oncogenic transformation by stimulating MAP kinase and PI3K signaling. PLoS One, 5, 11433. https://doi.org/10.1371/journal.pone.0011433
  16. Radhakrishnan VM, Putnam CW, Qi W, et al (2011). P53 suppresses expression of the 14-3-3 gamma oncogene. BMC Cancer, 11, 378. https://doi.org/10.1186/1471-2407-11-378
  17. Samuel T, Weber HO, Rauch P, et al (2001). The G2/M regulator 14-3-3sigma prevents apoptosis through sequestration of Bax. J Biol Chem, 276, 45201-06. https://doi.org/10.1074/jbc.M106427200
  18. Siegel R, Naishadham D, Jemal A (2012). Cancer statistics, 2012. CA Cancer J Clin, 62, 10-29. https://doi.org/10.3322/caac.20138
  19. Song X, Chen X, Yamaguchi H, et al (2006). Initiation of cofilin activity in response to EGF is uncoupled from cofilin phosphorylation and dephosphorylation in carcinoma cells. J Cell Sci, 119, 2871-81. https://doi.org/10.1242/jcs.03017
  20. Song Y, Yang Z, Ke Z, et al (2012). Expression of 14-3-3gamma in patients with breast cancer: correlation with clinicopathological features and prognosis. Cancer Epidemiol, 36, 533-6. https://doi.org/10.1016/j.canep.2012.05.003
  21. Umbricht CB, Evron E, Gabrielson E, et al (2001). Hypermethylation of 14-3-$3\sigma$ (stratifin) is an early event in breast cancer. Oncogene, 20, 3348-53. https://doi.org/10.1038/sj.onc.1204438
  22. Wang W, Shakes DC (1996). Molecular evolution of the 14-3-3 protein family. J Mol Evol, 43, 384-98. https://doi.org/10.1007/BF02339012
  23. Wu Q, Liu CZ, Tau LY, et al (2012). The clinicopathological and prognostic impact of 14-3-3 protein isoforms expression in human cholangiocarcinoma by immunohistochemistry. Asian Pac J Cancer Prev, 13, 1253-9. https://doi.org/10.7314/APJCP.2012.13.4.1253
  24. Xing H, Zhang S, Weinheimer C, et al (2000). 14-3-3 proteins block apoptosis and differentially regulate MAPK cascades. EMBO J, 19, 349-58. https://doi.org/10.1093/emboj/19.3.349
  25. Youlden DR, Cramb SM, Baade PD (2008). The international epidemiology of lung cancer: geographical distribution and secular trends. J Thorac Oncol, 3, 819-31. https://doi.org/10.1097/JTO.0b013e31818020eb
  26. Yu XY, Zhang Z, Zhang GJ, Guo KF, Kong CZ (2012). Knockdown of Cdc25B in renal cell carcinoma is associated with decreased malignant features. Asian Pac J Cancer Prev, 13, 931-5. https://doi.org/10.7314/APJCP.2012.13.3.931

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