DOI QR코드

DOI QR Code

RALY RNA Binding Protein-like Reduced Expression is Associated with Poor Prognosis in Clear Cell Renal Cell Carcinoma

  • Cui, Zhi-Wen (Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Centre) ;
  • Xia, Ye (Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Centre) ;
  • Ye, Yi-Wang (Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Centre) ;
  • Jiang, Zhi-Mao (Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Centre) ;
  • Wang, Ya-Dong (Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Centre) ;
  • Wu, Jian-Ting (Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Centre) ;
  • Sun, Liang (Department of Urology, Shenzhen Second People's Hospital) ;
  • Zhao, Jun (Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Centre) ;
  • Fa, Ping-Ping (Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Centre) ;
  • Sun, Xiao-Juan (The Institute of Urogenital Diseases, Shenzhen University) ;
  • Gui, Yao-Ting (Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Centre) ;
  • Cai, Zhi-Ming (Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Institute of Urology, Peking University Shenzhen Hospital, Shenzhen PKU-HKUST Medical Centre)
  • Published : 2012.07.31

Abstract

The molecular mechanisms involved in the progression of clear cell renal cell carcinomas (ccRCCs) are still unclear. The aim of this study was to analyse the relationships between expression of RALYL and clinical characteristics. In 41 paired samples of ccRCCs and adjacent normal tissues, we used real-time qPCR to evaluate the expression of RALYL mRNA. RALYL protein levels were determined in 146 samples of ccRCC and 37 adjacent normal tissues by immunohistochemistry. Statistical analysis was used to explore the relationships between expression of RALYL and the clinical characteristics (gender, age, tumor size, T stage, N stage, M stage, survival times and survival outcome) in ccRCC. In addition, these patients were follow-up period 64 months (range: 4~116months) to investigate the influence on prognosis. We found significantly differences between ccRCC tissues and normal tissues (p<0.001, paired-sample t test) in mRNA levels of RALYL. Immunohistochemistry analyses in 146 ccRCC samples and 37 adjacent normal tissues showed significantly lower RALYL protein levels in ccRCC samples (${\chi}^2$-test, p<0.001), inversely correlating with tumour size (p=0.024), T stage (0.005), N stage (p<0.001) as well as M stage (p=0.019), but not age (p=0.357) and gender (p=0.348). Kaplan-Meier survival analysis demonstrated that people with lower level of RALYL expression had a poorer survival rate than those with a higher level of RALYL expression, significantly different by the log-rank test (p=0.011). Cox regression analysis indicated that RALYL expression (p=0.039), N stage (p=0.008) and distant metastasis (p<0.001) were independent prognosis factors for the overall survival of ccRCC patients. We demonstrated that the expression of RALYL was significantly low in ccRCC and correlated with a poor prognosis in a large number of clinical samples. Our findings showed that RALYL may be a potential therapeutic target as well as a poor prognostic factor.

Keywords

References

  1. Baldewijns MM, van Vlodrop IJ, Vermeulen PB, et al (2010). VHL and HIF signalling in renal cell carcinogenesis. J Pathol, 221, 125-38. https://doi.org/10.1002/path.2689
  2. Banks RE, Craven RA, Harnden P, et al (2007). Key clinical issues in renal cancer: a challenge for proteomics. World J Urol, 25, 537-56. https://doi.org/10.1007/s00345-007-0199-y
  3. Bao S, Ouyang G, Bai X, et al (2004). Periostin potently promotes metastatic growth of colon cancer by augmenting cell survival via the Akt/PKB pathway. Cancer Cell, 5, 329-39. https://doi.org/10.1016/S1535-6108(04)00081-9
  4. Chen J, Cheng M, Yi L, Jiang CB (2011). Relationship between CYP1A1 genetic polymorphisms and renal cancer in China. Asian Pac J Cancer Prev, 12, 2163-6.
  5. Chow WH, Dong LM, Devesa SS, et al (2010). Epidemiology and risk factors for kidney cancer. Nat Rev Urol, 7, 245-57. https://doi.org/10.1038/nrurol.2010.46
  6. Cohen HT, McGovern FJ (2005). Renal-cell carcinoma. N Engl J Med, 353, 2477-90. https://doi.org/10.1056/NEJMra043172
  7. Eble JN, Sauter G, Ebstein J, Sesterhenn I (2004). Pathology and Genetics of Tumours of the Urinary System and Male Gential Organs. IARC-Press, Lyon 2004.
  8. Giordano TJ, Kuick R, Else T, et al (2009). Molecular classification and prognostication of adrenocortical tumors by transcriptome profiling. Clin Cancer Res, 15, 668-76. https://doi.org/10.1158/1078-0432.CCR-08-1067
  9. Grandinetti CA, Goldspiel BR (2007). Sorafenib and sunitinib: novel targeted therapies for renal cell cancer. Pharmacotherapy, 27, 1125-44. https://doi.org/10.1592/phco.27.8.1125
  10. Greene FL. AJCC cancer staging manual, Springer Verlag, 2002.
  11. Higgins JP, Shinghal R, Gill H, et al (2003). Gene expression patterns in renal cell carcinoma assessed by complementary DNA microarray. Am J Pathol, 162, 925-32. https://doi.org/10.1016/S0002-9440(10)63887-4
  12. Huang D, Ding Y, Luo WM, et al (2008). Inhibition of MAPK kinase signaling pathways suppressed renal cell carcinoma growth and angiogenesis in vivo. Cancer Res, 68, 81-8. https://doi.org/10.1158/0008-5472.CAN-07-5311
  13. Janzen NK, Kim HL, Figlin RA, Belldegrun AS (2003). Surveillance after radical or partial nephrectomy for localized renal cell carcinoma and management of recurrent disease. Urol Clin North Am, 30, 843-52. https://doi.org/10.1016/S0094-0143(03)00056-9
  14. Kroeze SG, Bijenhof AM, Bosch JL, Jans JJ (2010). Diagnostic and prognostic tissuemarkers in clear cell and papillary renal cell carcinoma. Cancer Biomark, 7, 261-8.
  15. Lee C, Iafrate AJ, Brothman AR (2007). Copy number variations and clinical cytogenetic diagnosis of constitutional disorders. Nat Genet, 39, S48-54. https://doi.org/10.1038/ng2092
  16. Levi F, Ferlay J, Galeone C, et al (2008). The changing pattern of kidney cancer incidence and mortality in Europe. BJU Int, 101, 949-58. https://doi.org/10.1111/j.1464-410X.2008.07451.x
  17. Maris JM, Mosse YP, Bradfield JP, et al (2008). Chromosome 6p22 locus associated with clinically aggressive neuroblastoma. N Engl J Med, 358, 2585-93. https://doi.org/10.1056/NEJMoa0708698
  18. Matsuura K, Nakada C, Mashio M, et al (2011). Downregulation of SAV1 plays a role in pathogenesis of high-grade clear cell renal cell carcinoma. BMC Cancer, 11, 523. https://doi.org/10.1186/1471-2407-11-523
  19. McCredie M (1994). Bladder and kidney cancers. Cancer Surv, 19, 343-68.
  20. Moran LB, Duke DC, Deprez M, et al (2006). Whole genome expression profiling of the medial and lateral substantia nigra in Parkinson's disease. Neurogenetics, 7, 1-11. https://doi.org/10.1007/s10048-005-0020-2
  21. Patard JJ, Rioux-Leclercq N, Masson D, et al (2009). Absence of VHL gene alteration and high VEGF expression are associated with tumour aggressiveness and poor survival of renal-cell carcinoma. Br J Cancer, 101, 1417-24. https://doi.org/10.1038/sj.bjc.6605298
  22. Saussez S, Cucu DR, Decaestecker C, et al (2006). Galectin 7 (p53-induced gene 1): a new prognostic predictor of recurrence and survival in stage IV hypopharyngeal cancer. Ann Surg Oncol, 13, 999-1009. https://doi.org/10.1245/ASO.2006.08.033
  23. Shyamsundar R, Kim YH, Higgins JP, et al (2005). A DNA microarray survey of gene expression in normal human tissues. Genome Biol, 6, R22. https://doi.org/10.1186/gb-2005-6-3-r22
  24. Song T, Zhang X, Wang C, et al (2011). MiR-138 suppresses expression of hypoxia-inducible factor $1\alpha\;(HIF-1\alpha)$ in clear cell renal cell carcinoma 786-O cells. Asian Pac J Cancer Prev, 12, 1307-11.
  25. Soulitzis N, Karyotis I, Delakas D, Spandidos DA (2006). Expression analysis of peptide growth factors VEGF, FGF2, TGFB1, EGF and IGF1 in prostate cancer and benign prostatic hyperplasia. Int J Oncol, 29, 305-14.
  26. Tsuchiya A, Sakamoto M, Yasuda J, et al (2003). Expression profiling in ovarian clear cell carcinoma: identification of hepatocyte nuclear factor-$1\beta$ as a molecular marker and a possible molecular target for therapy of ovarian clear cell carcinoma. Am J Pathol, 163, 2503-12. https://doi.org/10.1016/S0002-9440(10)63605-X
  27. Vaziri SA, Grabowski DR, Hill J, et al (2009). Inhibition of proteasome activity by bortezomib in renal cancer cells is p53 dependent and VHL independent. Anticancer Res, 29, 2961-9.
  28. Wu S, Wang Y, Sun L, et al (2011). Decreased expression of dual-specificity phosphatase 9 is associated with poor prognosis in clear cell renal cell carcinoma. BMC Cancer, 11, 413. https://doi.org/10.1186/1471-2407-11-413
  29. Yang JC, Haworth L, Sherry RM, et al (2003). A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med, 349, 427-34. https://doi.org/10.1056/NEJMoa021491
  30. Yang Y, Li Y, Huang XE, Lu YY, Wu XY (2011). Exploration of cancer pain treatment by morphine infusion through an embedded device. Asian Pac J Cancer Prev, 12, 3151-2.
  31. Young AN, Amin MB, Moreno CS, et al (2001). Expression profiling of renal epithelial neoplasms: a method for tumor classification and discovery of diagnostic molecular markers. Am J Pathol, 158, 1639-51. https://doi.org/10.1016/S0002-9440(10)64120-X

Cited by

  1. A Genome Wide Association Study for Longevity in Cattle vol.04, pp.01, 2014, https://doi.org/10.4236/ojgen.2014.41007