Skip to main content

Advertisement

Log in

Elevated Expression of N-Acetylgalactosaminyltransferase 10 Predicts Poor Survival and Early Recurrence of Patients with Clear-Cell Renal Cell Carcinoma

  • Urologic Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Purpose

The aim of this study was to evaluate the potential prognostic significance of N-acetylgalactosaminyltransferase 10 (GALNT10) in patients with clear-cell renal cell carcinoma (ccRCC) after surgical resection.

Methods

We retrospectively enrolled 271 patients (202 in the training cohort and 69 in the validation cohort) with ccRCC undergoing nephrectomy at a single institution. Clinicopathologic features, overall survival (OS), and recurrence-free survival (RFS) were recorded. GALNT10 intensities were assessed by immunohistochemistry in the specimens of patients. The Kaplan–Meier method was applied to compare survival curves. Cox regression models were used to analyze the impact of prognostic factors on OS and RFS. Concordance index (C-index) was calculated to assess predictive accuracy.

Results

In both cohorts, elevated GALNT10 expression in tumor tissues positively correlated with advanced TNM stage. High GALNT10 expression indicated poor survival and early recurrence of patients with ccRCC, particularly with early-stage disease. After backward elimination, GALNT10 expression was identified as an independent adverse prognostic factor for survival and recurrence. The predictive accuracy of TNM, University of California Los Angeles Integrated Staging System, and stage, size, grade, and necrosis prognostic models was improved when GALNT10 expression was added.

Conclusions

GALNT10 expression is a potential independent adverse prognostic biomarker for recurrence and survival of patients with ccRCC after nephrectomy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

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. Yang L, Parkin DM, Ferlay J, Li L, Chen Y. Estimates of cancer incidence in China for 2000 and projections for 2005. Cancer Epidemiol Biomark Prev. 2005;14(1):243–250.

    PubMed  Google Scholar 

  3. Joseph RW, Kapur P, Serie DJ, et al. Loss of BAP1 protein expression is an independent marker of poor prognosis in patients with low-risk clear cell renal cell carcinoma. Cancer. 2013;120(7):1059–67.

    Article  PubMed Central  PubMed  Google Scholar 

  4. Stewart GD, O’Mahony FC, Powles T, Riddick AC, Harrison DJ, Faratian D. What can molecular pathology contribute to the management of renal cell carcinoma? Nat Rev Urol. 2011;8(5):255–65.

    Article  CAS  PubMed  Google Scholar 

  5. Lang H, Lindner V, de Fromont M, et al. Multicenter determination of optimal interobserver agreement using the Fuhrman grading system for renal cell carcinoma: assessment of 241 patients with >15-year follow-up. Cancer. 2005;103(3):625–9.

    Article  PubMed  Google Scholar 

  6. Zhao H, Ljungberg B, Grankvist K, Rasmuson T, Tibshirani R, Brooks JD. Gene expression profiling predicts survival in conventional renal cell carcinoma. PLoS Med. 2006;3(1):e13.

    Article  PubMed Central  PubMed  Google Scholar 

  7. Sim SH, Messenger MP, Gregory WM, et al. Prognostic utility of pre-operative circulating osteopontin, carbonic anhydrase IX and CRP in renal cell carcinoma. Br J Cancer. 2012;107(7):1131–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Zisman A, Pantuck AJ, Dorey F, et al. Improved prognostication of renal cell carcinoma using an integrated staging system. J Clin Oncol. 2001;19(6):1649–57.

    CAS  PubMed  Google Scholar 

  9. Frank I, Blute ML, Cheville JC, Lohse CM, Weaver AL, Zincke H. An outcome prediction model for patients with clear cell renal cell carcinoma treated with radical nephrectomy based on tumor stage, size, grade and necrosis: the SSIGN score. J Urol. 2002;168(6):2395–400.

    Article  PubMed  Google Scholar 

  10. Sun M, Shariat SF, Cheng C, et al. Prognostic factors and predictive models in renal cell carcinoma: a contemporary review. Eur Urol. 2011;60(4):644–61.

    Article  PubMed  Google Scholar 

  11. Brockhausen I. Pathways of O-glycan biosynthesis in cancer cells. Biochim Biophys Acta. 1999;1473(1):67–95.

    Article  CAS  PubMed  Google Scholar 

  12. Hollingsworth MA, Swanson BJ. Mucins in cancer: protection and control of the cell surface. Nat Rev Cancer. 2004;4(1):45–60.

    Article  CAS  PubMed  Google Scholar 

  13. Ten Hagen KG, Fritz TA, Tabak LA. All in the family: the UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferases. Glycobiology. 2003;13(1):1R–16R.

    Article  PubMed  Google Scholar 

  14. Kitada S, Yamada S, Kuma A, et al. Polypeptide N-acetylgalactosaminyl transferase 3 independently predicts high-grade tumours and poor prognosis in patients with renal cell carcinomas. Br J Cancer. 2013;109(2):472–81.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Ishikawa M, Kitayama J, Nariko H, Kohno K, Nagawa H. The expression pattern of UDP-N-acetyl-alpha-d-galactosamine: polypeptide N-acetylgalactosaminyl transferase-3 in early gastric carcinoma. J Surg Oncol. 2004;86(1):28–33.

    Article  CAS  PubMed  Google Scholar 

  16. Gu C, Oyama T, Osaki T, et al. Low expression of polypeptide GalNAc N-acetylgalactosaminyl transferase-3 in lung adenocarcinoma: impact on poor prognosis and early recurrence. Br J Cancer. 2004;90(2):436–42.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Yamamoto S, Nakamori S, Tsujie M, et al. Expression of uridine diphosphate N-acetyl-alpha-d-galactosamine: polypeptide N-acetylgalactosaminyl transferase 3 in adenocarcinoma of the pancreas. Pathobiology. 2004;71(1):12–8.

    Article  PubMed  Google Scholar 

  18. Berois N, Mazal D, Ubillos L, et al. UDP-N-acetyl-d-galactosamine: polypeptide N-acetylgalactosaminyltransferase-6 as a new immunohistochemical breast cancer marker. J Histochem Cytochem. 2006;54(3):317–28.

    Article  CAS  PubMed  Google Scholar 

  19. Park JH, Nishidate T, Kijima K, et al. Critical roles of mucin 1 glycosylation by transactivated polypeptide N-acetylgalactosaminyltransferase 6 in mammary carcinogenesis. Cancer Res. 2010;70(7):2759–69.

    Article  CAS  PubMed  Google Scholar 

  20. Li Z, Yamada S, Inenaga S, et al. Polypeptide N-acetylgalactosaminyltransferase 6 expression in pancreatic cancer is an independent prognostic factor indicating better overall survival. Br J Cancer. 2011;104(12):1882–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  21. Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010;17(6):1471–4.

    Article  PubMed  Google Scholar 

  22. Zhu XD, Zhang JB, Zhuang PY, et al. 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. 2008;26(16):2707–16.

    Article  PubMed  Google Scholar 

  23. Detre S, Saclani Jotti G, Dowsett M. A “quickscore” method for immunohistochemical semiquantitation: validation for oestrogen receptor in breast carcinomas. J Clin Pathol. 1995;48(9):876–8.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Camp RL, Dolled-Filhart M, Rimm DL. X-tile: a new bio-informatics tool for biomarker assessment and outcome-based cut-point optimization. Clin Cancer Res. 2004;10(21):7252–9.

    Article  CAS  PubMed  Google Scholar 

  25. Hakomori S. Glycosylation defining cancer malignancy: new wine in an old bottle. Proc Natl Acad Sci USA. 2002;99(16):10231–3.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Dube DH, Bertozzi CR. Glycans in cancer and inflammation–potential for therapeutics and diagnostics. Nat Rev Drug Discov. 2005;4(6):477–88.

    Article  CAS  PubMed  Google Scholar 

  27. Gaziel-Sovran A, Segura MF, Di Micco R, et al. miR-30b/30d regulation of GalNAc transferases enhances invasion and immunosuppression during metastasis. Cancer Cell. 2011;20(1):104–18.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  28. Liu J, Liu H, Zhang W, et al. N-acetylglucosaminyltransferase V confers hepatoma cells with resistance to anoikis through EGFR/PAK1 activation. Glycobiology. 2013;23(9):1097–109.

    Article  PubMed  Google Scholar 

  29. Onitsuka K, Shibao K, Nakayama Y, et al. Prognostic significance of UDP-N-acetyl-alpha-d-galactosamine:polypeptide N-acetylgalactosaminyltransferase-3 (GalNAc-T3) expression in patients with gastric carcinoma. Cancer Sci. 2003;94(1):32–6.

    Article  CAS  PubMed  Google Scholar 

  30. Taniuchi K, Cerny RL, Tanouchi A, et al. Overexpression of GalNAc-transferase GalNAc-T3 promotes pancreatic cancer cell growth. Oncogene. 2011;30(49):4843–54.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Cheng L, Tachibana K, Zhang Y, et al. Characterization of a novel human UDP-GalNAc transferase, pp-GalNAc-T10. FEBS Lett. 2002;531(2):115–21.

    Article  CAS  PubMed  Google Scholar 

  32. Gao Y, Liu Z, Feng J, et al. Expression pattern of polypeptide N-acetylgalactosaminyltransferase-10 in gastric carcinoma. Oncol Lett. 2012;5(1):113–6.

    PubMed Central  PubMed  Google Scholar 

  33. Wu YM, Liu CH, Hu RH, et al. Mucin glycosylating enzyme GALNT2 regulates the malignant character of hepatocellular carcinoma by modifying the EGF receptor. Cancer Res. 2012;71(23):7270–9.

    Article  Google Scholar 

  34. Merlin J, Stechly L, de Beauce S, et al. Galectin-3 regulates MUC1 and EGFR cellular distribution and EGFR downstream pathways in pancreatic cancer cells. Oncogene. 2011;30(22):2514–25.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgment

This work was supported by grants from the National Basic Research Program of China (2012CB822104), the National Key Projects for Infectious Diseases of China (2012ZX10002-012), the National Natural Science Foundation of China (31100629, 31270863, 81471621, 81472227), the Program for New Century Excellent Talents in University (NCET-13-0146), and the Shanghai Rising-Star Program (13QA1400300). All these study sponsors had no role in the study design, or in the collection, analysis, and interpretation of data. We thank Ms. Haiying Zeng (Department of Pathology, Zhongshan Hospital, Shanghai Medical College of Fudan University) for technical assistance.

Disclosure

The authors have declared no conflicts of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jiejie Xu MD, PhD.

Additional information

Qian Wu, Liu Yang, and Haiou Liu have contributed equally to this work.

Electronic supplementary material

Below is the link to the electronic supplementary material.

10434_2014_4236_MOESM1_ESM.tif

Figure S1. N-acetylgalactosaminyltransferase 10 (GALNT10) expression in clear-cell renal cell carcinoma (ccRCC) patients. (a, b) Representative immunohistochemical (IHC) photographs of GALNT10 staining in ccRCC patients with both peri-tumor and tumor tissues (a), or tumor tissues dichotomize as low and high (b). Arrows indicate positive staining of GALNT10 in each image (original magnification x 200). Scale bar: 50 um. (c) Scatter plots for 107 paired peri-tumor and tumor tissues of IHC staining score. P value is determined by paired t test. (d) The patient percentage of high GALNT10 staining increased gradually acompanied with disease progression from TNM stage I to IV (TIFF 14185 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wu, Q., Yang, L., Liu, H. et al. Elevated Expression of N-Acetylgalactosaminyltransferase 10 Predicts Poor Survival and Early Recurrence of Patients with Clear-Cell Renal Cell Carcinoma. Ann Surg Oncol 22, 2446–2453 (2015). https://doi.org/10.1245/s10434-014-4236-y

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-014-4236-y

Keywords

Navigation