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Received: 2009-08-13

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Journal of Zhejiang University SCIENCE B 2010 Vol.11 No.2 P.136-143


Nicotinamide N-methyltransferase protein expression in renal cell cancer

Author(s):  Jun ZHANG, Xin-you XIE, Su-wen YANG, Jin WANG, Chao HE

Affiliation(s):  Department of Clinical Laboratory, Sir Run Run Show Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, China; more

Corresponding email(s):   jameszhang2000@163.com, drhe_srrsh@sina.com

Key Words:  Nicotinamide N-methyltransferase, Monoclonal antibody, Tumor biomarker, Renal cell cancer

Jun ZHANG, Xin-you XIE, Su-wen YANG, Jin WANG, Chao HE. Nicotinamide N-methyltransferase protein expression in renal cell cancer[J]. Journal of Zhejiang University Science B, 2010, 11(2): 136-143.

@article{title="Nicotinamide N-methyltransferase protein expression in renal cell cancer",
author="Jun ZHANG, Xin-you XIE, Su-wen YANG, Jin WANG, Chao HE",
journal="Journal of Zhejiang University Science B",
publisher="Zhejiang University Press & Springer",

%0 Journal Article
%T Nicotinamide N-methyltransferase protein expression in renal cell cancer
%A Xin-you XIE
%A Su-wen YANG
%A Chao HE
%J Journal of Zhejiang University SCIENCE B
%V 11
%N 2
%P 136-143
%@ 1673-1581
%D 2010
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B0900249

T1 - Nicotinamide N-methyltransferase protein expression in renal cell cancer
A1 - Jun ZHANG
A1 - Xin-you XIE
A1 - Su-wen YANG
A1 - Jin WANG
A1 - Chao HE
J0 - Journal of Zhejiang University Science B
VL - 11
IS - 2
SP - 136
EP - 143
%@ 1673-1581
Y1 - 2010
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B0900249

Objective: To understand the function of nicotinamide N-methyltransferase (NNMT) protein as tumor biomarker in renal carcinoma. Methods: Recombinant NNMT protein was used to prepare monoclonal antibodies by hybridoma technique. The diagnostic and prognostic function of NNMT protein in renal carcinoma was evaluated by analyzing 74 renal cancer tissues through immunohistochemical staining for NNMT by using the prepared antibodies. Results: Two hybridomas named 2F8 and 1E7 stably secreting the monoclonal antibodies were isolated successfully, and characters such as isotypes and specificity were determined. NNMT protein was significantly up-regulated in renal cancer and significantly associated with tumor histology and ages. The univariate survival analysis demonstrated that the pT-status, high levels of NNMT, and distant metastasis were significant prognosticators. Conclusion: NNMT is over-expressed in a large proportion in renal cell cancers. High NNMT expression is significantly associated with unfavorable prognosis. However, the prognostic value of NNMT needs further verification in larger sample sizes.

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article


[1] Aksoy, S., Szumlanski, C.L., Weinshilboum, R.M., 1994. Human liver nicotinamide N-methyltransferase: cDNA cloning, expression, and biochemical characterization. J. Biol. Chem., 269:14835-14840.

[2] Aoyama, K., Matsubara, K., Kondo, M., Murakawa, Y., Suno, M., Yamashita, K., Yamaguchi, S., Kobayashi, S., 2001. Nicotinamide N-methyltransferase is higher in the lumbar cerebrospinal fluid of patients with Parkinson’s disease. Neurosci. Lett., 298(1):78-80.

[3] Cohen, H., McGovern, F., 2005. Renal-cell carcinoma. N. Engl. J. Med., 353(23):2477-2490.

[4] Eble, J.N., Sauter, G., Epstein, J.I., Sesterhenn, I.A., 2004. World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs. IARC Press, Lyon, p.10-32.

[5] Eun, J.P., Choi, H.Y., Kwak, Y.G., 2004. Proteomic analysis of human cerebral cortex in epileptic patients. Exp. Mol. Med., 36:185-191.

[6] Ficarra, V., Galfano, A., Mancini, M., Martignoni, G., Artibani, W., 2007. TNM staging system for renal-cell carcinoma: current status and future perspectives. Lancet Oncol., 8(6):554-558.

[7] Fritzsche, F.R., Riener, M.O., Dietel, M., Moch, H., Jung, K., Kristiansen, G., 2008. GOLPH2 expression in renal cell cancer. BMC Urology, 8(1):15.

[8] Hanash, S., 2003. Disease proteomics. Nature, 422(6928):226-232.

[9] Horiguchi, A., Oya, M., Shimada, T., Uchida, A., Marumo, K., Murai, M., 2002. Activation of signal transducer and activator of transcription 3 in renal cell carcinoma: a study of incidence and its association with pathological features and clinical outcome. J. Urol., 168(2):762-765.

[10] Jang, J.S., Cho, H.Y., Lee, Y.J., Ha, W.S., Kim, H.W., 2004. The differential proteome profile of stomach cancer: identification of the biomarker candidates. Oncol. Res., 14:491-499.

[11] Jemal, A., Siegel, R., Ward, E., Murray, T., Xu, J., Thun, M.J., 2007. Cancer statistics, 2007. CA: A Cancer Journal for Clinicians, 57(1):43-66.

[12] Kim, J., Hong, S.J., Lim, E.K., Yu, Y.S., Kim, S.W., Roh, J.H., Do, I.G., Joh, J.W., Kim, D.S., 2009. Expression of nicotinamide N-methyltransferase in hepatocellular carcinoma is associated with poor prognosis. J. Exp. Clin. Cancer Res., 28(1):20.

[13] Lim, B.H., Cho, B.I., Kim, Y.N., Kim, J.W., Park, S.T., Lee, C.W., 2006. Overexpression of nicotinamide N-methyltransferase in gastric cancer tissues and its potential post-translational modification. Exp. Mol. Med., 38:455-465.

[14] Ma, C.F., Zhang, J., Xie, X.Y., 2006. Construction of recombinant plasmid nicotinamide N-methyltransferase gene and expression in E. coli. J. Zhejiang Med., 28(1):10-12 (in Chinese).

[15] McLaughlin, J.K., Lipworth, L., 2000. Epidemiologic aspects of renal cell cancer. Seminars in Oncology, 27:115-123.

[16] Papworth, K., Bergh, A., Grankvist, K., Ljungberg, B., Rasmuson, T., 2009. Expression of erythropoietin and its receptor in human renal cell carcinoma. Tumor Biol., 30(2):86-92.

[17] Rini, J., Szumlanski, C., Guerciolini, R., Weinshilboum, R.M., 1990. Human liver nicotinamide N-methyltransferase: ion-pairing radiochemical assay, biochemical properties and individual variation. Clin. Chim. Acta, 186(3):359-374.

[18] Roessler, M., Rollinger, W., Palme, S., Hagmann, M.L., Berndt, P., Engel, A.M., Schneidinger, B., Pfeffer, M., Andres, H., Karl, J., et al., 2005. Identification of nicotinamide N-methyltransferase as a novel serum tumor marker for colorectal cancer. Clin. Cancer Res., 11(18):6550-6557.

[19] Sartini, D., Muzzonigro, G., Milanese, G., Pierella, F., Rossi, V., Emanuelli, M., 2006. Identification of nicotinamide N-methyltransferase as a novel tumor marker for renal clear cell carcinoma. J. Urol., 176(5):2248-2254.

[20] Sartini, D., Santarelli, A., Rossi, V., Goteri, G., Rubini, C., Ciavarella, D., Muzio, L., Emanuelli, M., 2007. Nicotinamide N-methyltransferase upregulation inversely correlates with lymph node metastasis in oral squamous cell carcinoma. Mol. Med., 13(7-8):415-421.

[21] Tomida, M., Ohtake, H., Yokota, T., Kobayashi, Y., Kurosumi, M., 2008. Stat3 up-regulates expression of nicotinamide N-methyltransferase in human cancer cells. J. Cancer Res. Clin. Oncol., 134(5):551-559.

[22] Tomida, M., Mikami, I., Takeuchi, S., Nishimura, H., Akiyama, H., 2009. Serum levels of nicotinamide N-methyltransferase in patients with lung cancer. J. Cancer Res. Clin. Oncol., 135(9):123-1229.

[23] Xu, J., Moatamed, F., Caldwell, J.S., Walker, J.R., Kraiem, Z., Taki, K., Brent, G.A., Hershman, J.M., 2003. Enhanced expression of nicotinamide N-methyltransferase in human papillary thyroid carcinoma cells. J. Clin. Endocrinol. Metab., 88(10):4990-4996.

[24] Xu, J., Capezzone, M., Xu, X., Hershman, J.M., 2005. Activation of nicotinamide N-methyltransferase gene promoter by hepatocyte nuclear factor-1beta in human papillary thyroid cancer cells. Mol. Endocrinol., 19(2):527-539.

[25] Yan, L., Otterness, D.M., Weinshilboum, R.M., 1999. Human nicotinamide N-methyltransferase pharmacogenetics: gene sequence analysis and promoter characterization. Pharmacogenetics, 9(3):307-316.

[26] Yao, M., Tabuchi, H., Nagashima, Y., Baba, M., Nakaigawa, N., Ishiguro, H., Hamada, K., Inayama, Y., Kishida, T., Hattori, K., et al., 2005. Gene expression analysis of renal carcinoma: adipose differentiation-related protein as a potential diagnostic and prognostic biomarker for clear-cell renal carcinoma. J. Pathol., 205(3):377-387.

[27] Zhang, J., 2003. Are poly(ADP-ribosyl)ation by PARP-1 and deacetylation by Sir2 linked? BioEssays, 25(8):808-814.

[28] Zhang, J.B., Lu, X.M., Wei, H.P., Cheng, L.Y., He, J., Zhang, Z.P., Zhang, X.E., Yu, Z.N., 2008. Production and characterization of monoclonal antibodies to nucleoprotein of Marburg virus. Hybridoma, 27(6):423-429.

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