DOI QR코드

DOI QR Code

ST6Gal-I Predicts Postoperative Clinical Outcome for Patients with Localized Clear-cell Renal Cell Carcinoma

  • Liu, Hai-Ou (Key Laboratory of Glycoconjugate Research, MOH, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University) ;
  • Wu, Qian (Key Laboratory of Glycoconjugate Research, MOH, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University) ;
  • Liu, Wei-Si (Key Laboratory of Glycoconjugate Research, MOH, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University) ;
  • Liu, Yi-Dong (Key Laboratory of Glycoconjugate Research, MOH, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University) ;
  • Fu, Qiang (Key Laboratory of Glycoconjugate Research, MOH, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University) ;
  • Zhang, Wei-Juan (Department of Immunology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University) ;
  • Xu, Le (Department of Urology, Zhongshan Hospital, Shanghai Medical College of Fudan University) ;
  • Xu, Jie-Jie (Key Laboratory of Glycoconjugate Research, MOH, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Shanghai Medical College of Fudan University)
  • 발행 : 2015.01.06

초록

Hyperactivated ${\alpha}2$-6-sialylation on N-glycans due to overexpression of the Golgi enzyme ${\beta}$-galactoside: ${\alpha}2$-6-sialyltransferase (ST6Gal-I) often correlates with cancer progression, metastasis, and poor prognosis. This study was aimed to determine the association between ST6Gal-I expression and the risk of recurrence and survival of patients with localized clear-cell renal cell carcinoma (ccRCC) following surgery. We retrospectively enrolled 391 patients (265 in training cohort and 126 in validation cohort) with localized ccRCC underwent nephrectomy at a single center. Tissue microarrays were constructed for immunostaining of ST6Gal-I. Prognostic value and clinical outcomes were evaluated. High ST6Gal-I expression was associated with Fuhrman grade (p<0.001 and p=0.016, respectively) and the University of California Los-Angeles Integrated Staging System (UISS) score (p=0.004 and p=0.017, respectively) in both cohorts. Patients with high ST6Gal-I expression had significantly worse overall survival (OS) (p<0.001 and p<0.001, respectively) and recurrence free survival (RFS) (p<0.001 and p=0.002, respectively) than those with low expression in both cohorts. On multivariate analysis, ST6Gal-I expression remained associated with OS and RFS even after adjusting for the UISS score. Stratified analysis suggested that the association is more pronounced among patients with low and intermediate-risk disease defined by the UISS score. High ST6Gal-I expression is a potential independent adverse predictor of survival and recurrence in ccRCC patients, and the prognostic value is most prominent in those with low and intermediate-risk disease defined by the UISS score.

키워드

참고문헌

  1. Almaraz RT, Tian Y, Bhattarcharya R, et al (2014). Metabolic flux increases glycoprotein sialylation: implications for cell adhesion and cancer metastasis. Mol Cell Proteomics, 11, 112.
  2. Borzym-Kluczyk M, Radziejewska I (2013). Changes of the expression of Lewis blood group antigens in glycoproteins of renal cancer tissues. Acta Biochim Pol, 60, 223-6.
  3. Brugarolas J (2014). Molecular genetics of clear-cell renal cell carcinoma. J Clin Oncol, 32, 1968-76. https://doi.org/10.1200/JCO.2012.45.2003
  4. Bull C, Boltje TJ, Wassink M, et al (2013). Targeting aberrant sialylation in cancer cells using a fluorinated sialic acid analog impairs adhesion, migration, and in vivo tumor growth. Mol Cancer Ther, 12, 1935-46. https://doi.org/10.1158/1535-7163.MCT-13-0279
  5. Bull C, Stoel MA, den Brok MH, et al (2014). Sialic acids sweeten a tumor's life. Cancer Res, 74, 3199-204. https://doi.org/10.1158/0008-5472.CAN-14-0728
  6. Dall'Olio F (2000). The sialyl-alpha2, 6-lactosaminyl-structure: biosynthesis and functional role. Glycoconj J, 17, 669-76. https://doi.org/10.1023/A:1011077000164
  7. Escudier B, Eisen T, Porta C, et al (2012). Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol, 23, 65-71. https://doi.org/10.1093/annonc/mdr034
  8. Escudier B, Kataja V (2010). Renal cell carcinoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol, 21, 137-9. https://doi.org/10.1093/annonc/mdq206
  9. Harduin-Lepers A, Vallejo-Ruiz V, Krzewinski-Recchi MA, et al (2001). The human sialyltransferase family. Biochimie, 83, 727-37. https://doi.org/10.1016/S0300-9084(01)01301-3
  10. Harrell FE, Jr., Lee KL, Mark DB (1996). Multivariable prognostic models: issues in developing models, evaluating assumptions and adequacy, and measuring and reducing errors. Stat Med, 15, 361-87. https://doi.org/10.1002/(SICI)1097-0258(19960229)15:4<361::AID-SIM168>3.0.CO;2-4
  11. Hedlund M, Ng E, Varki A, et al (2008). alpha 2-6-Linked sialic acids on N-glycans modulate carcinoma differentiation in vivo. Cancer Res, 68, 388-94. https://doi.org/10.1158/0008-5472.CAN-07-1340
  12. Kannagi R (2004). Molecular mechanism for cancer-associated induction of sialyl Lewis X and sialyl Lewis A expression-The Warburg effect revisited. Glycoconj J, 20, 353-64.
  13. Lee M, Park JJ, Ko YG, et al (2012). Cleavage of ST6Gal I by radiation-induced BACE1 inhibits golgi-anchored ST6Gal I-mediated sialylation of integrin beta1 and migration in colon cancer cells. Radiat Oncol, 7, 47. https://doi.org/10.1186/1748-717X-7-47
  14. Li B, Qiu B, Lee DS, et al (2014). Fructose-1, 6-bisphosphatase opposes renal carcinoma progression. Nature, 513, 251-5. https://doi.org/10.1038/nature13557
  15. Liu Z, Swindall AF, Kesterson RA, et al (2011). ST6Gal-I regulates macrophage apoptosis via alpha2-6 sialylation of the TNFR1 death receptor. J Biol Chem, 286, 39654-62. https://doi.org/10.1074/jbc.M111.276063
  16. Lotan Y, Bagrodia A, Passoni N, et al (2013). Prospective evaluation of a molecular marker panel for prediction of recurrence and cancer-specific survival after radical cystectomy. Eur Urol, 64, 465-71. https://doi.org/10.1016/j.eururo.2013.03.043
  17. Motzer RJ, Agarwal N, Beard C, et al (2009). NCCN clinical practice guidelines in oncology: kidney cancer. J Natl Compr Canc Netw, 7, 618-30.
  18. Network CGAR (2013). Comprehensive molecular characterization of clear cell renal cell carcinoma. Nature, 499, 43-9. https://doi.org/10.1038/nature12222
  19. Philips GK, Atkins MB (2014). New agents and new targets for renal cell carcinoma. Am Soc Clin Oncol Educ Book, 222-7.
  20. Preston RS, Philp A, Claessens T, et al (2011). Absence of the Birt-Hogg-Dube gene product is associated with increased hypoxia-inducible factor transcriptional activity and a loss of metabolic flexibility. Oncogene, 30, 1159-73. https://doi.org/10.1038/onc.2010.497
  21. Seales EC, Jurado GA, Singhal A, et al (2003). Ras oncogene directs expression of a differentially sialylated, functionally altered beta1 integrin. Oncogene, 22, 7137-45. https://doi.org/10.1038/sj.onc.1206834
  22. Swindall AF, Bellis SL (2011). Sialylation of the Fas death receptor by ST6Gal-I provides protection against Fasmediated apoptosis in colon carcinoma cells. J Biol Chem, 286, 22982-90. https://doi.org/10.1074/jbc.M110.211375
  23. Swindall AF, Londono-Joshi AI, Schultz MJ, et al (2013). ST6Gal-I protein expression is upregulated in human epithelial tumors and correlates with stem cell markers in normal tissues and colon cancer cell lines. Cancer Res, 73, 2368-78. https://doi.org/10.1158/0008-5472.CAN-12-3424
  24. Tanriverdi O (2013). Review on targeted treatment of patients with advanced-stage renal cell carcinoma: a medical oncologist's perspective. Asian Pac J Cancer Prev, 14, 609-17. https://doi.org/10.7314/APJCP.2013.14.2.609
  25. Wang X, He H, Zhang H, et al (2013). Clinical and prognostic implications of beta1, 6-N-acetylglucosaminyltransferase V in patients with gastric cancer. Cancer Sci, 104, 185-93. https://doi.org/10.1111/cas.12049
  26. Zhu XD, Zhang JB, Zhuang PY, et al (2008). High expression of macrophage colony-stimulating factor in peritumoral liver tissue is associated with poor survival after curative resection of hepatocellular carcinoma. J Clin Oncol, 26, 2707-16. https://doi.org/10.1200/JCO.2007.15.6521
  27. Zhuo Y, Bellis SL (2011). Emerging role of alpha2, 6-sialic acid as a negative regulator of galectin binding and function. J Biol Chem, 286, 5935-41. https://doi.org/10.1074/jbc.R110.191429
  28. Zisman A, Pantuck AJ, Wieder J, et al (2002). Risk group assessment and clinical outcome algorithm to predict the natural history of patients with surgically resected renal cell carcinoma. J Clin Oncol, 20, 4559-66. https://doi.org/10.1200/JCO.2002.05.111

피인용 문헌

  1. α2,6-Sialylation mediates hepatocellular carcinoma growth in vitro and in vivo by targeting the Wnt/β-catenin pathway vol.6, pp.5, 2017, https://doi.org/10.1038/oncsis.2017.40