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.
Similar content being viewed by others
References
Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63(1):11–30.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Brockhausen I. Pathways of O-glycan biosynthesis in cancer cells. Biochim Biophys Acta. 1999;1473(1):67–95.
Hollingsworth MA, Swanson BJ. Mucins in cancer: protection and control of the cell surface. Nat Rev Cancer. 2004;4(1):45–60.
Ten Hagen KG, Fritz TA, Tabak LA. All in the family: the UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferases. Glycobiology. 2003;13(1):1R–16R.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Hakomori S. Glycosylation defining cancer malignancy: new wine in an old bottle. Proc Natl Acad Sci USA. 2002;99(16):10231–3.
Dube DH, Bertozzi CR. Glycans in cancer and inflammation–potential for therapeutics and diagnostics. Nat Rev Drug Discov. 2005;4(6):477–88.
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.
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.
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.
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.
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.
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.
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.
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.
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
Corresponding author
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
About this article
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
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1245/s10434-014-4236-y