Increased Nuclear NDRG1 Expression in Prostate Cancer and Positively Associated with Increasing Gleason Grade and Stage, While Decreased Membranous and Cytoplasmic NDRG1 Expression in Prostate Cancer
Keywords:
Prostate cancer, NDRG1, ImmunohistochemistryAbstract
Summary Background: Prostate cancer has few prognostic biomarkers, and differential diagnosis and prognosis of aggressive versus non-aggressive tumors can be challenging clinically. Aims: This study aims to investigate the hypothesis that NDRG1 might be a potential biomarker for prostate tumor and could distinguish between aggressive tumors requiring radical intervention and those that have a good prognosis. It is thought to be a potential biomarker that can predict the clinical progression and prognosis of different kinds of tumors. However, its role in prostate cancer remains unclear. Materials and methods: NDRG1 expression has been evaluated by immunohistochemistry using a tissue microarray cohort with 96 cases including normal, adjacent normal and malignant prostate tissues. Results: This study showed nuclear, cytoplasmic and membranous NDRG1 immunostaining in both normal and malignant prostate tissues. Reduction of membranous and increased nucleocytoplasmic NDRG1 staining is shown in prostate cancer compared to normal prostate and is positively associated with increasing primary Gleason grade, but not with clinical stage. Nuclear NDRG1 staining is increased significantly in prostate cancer and is positively associated with increasing primary Gleason grade and clinical stage. In contrast, cytoplasmic NDRG1 staining is decreased significantly in prostate cancer compared to normal prostate, but not associated with other clinical features. Conclusion: This preliminary data suggests that NDRG1 may have a role in cancer development and/or aggressiveness and warrants further investigation to understand its function and establish if it could be a potential diagnostic biomarker for prostate cancer.References
Lang, S.H.; Frame, F.M. & Collins, A.T. Prostate cancer stem cells. The Journal of pathology, 2009, 217(2), pp. 299-306.
Kirby, R.S. Prostate cancer. 7th ed.; Abingdon: Abingdon: Health Press, 2012.
Bagnall, P. Diagnosis and treatment of prostate cancer. Nursing times, 2014, 110(9), p. 12.
Dunn, M.W. & Kazer, M.W. Prostate Cancer Overview. Seminars in Oncology Nursing, 2011, 27(4), pp. 241-250.
Qu, M.; Ren, S.C. & Sun, Y.H. Current early diagnostic biomarkers of prostate cancer. Asian journal of andrology, 2014, 16(4), pp. 549-54.
Li, Y., Pan, P., Qiao, P. & Liu, R. Downregulation of N-myc downstream regulated gene 1 caused by the methylation of CpG islands of NDRG1 promoter promotes proliferation and invasion of prostate cancer cells. International journal of oncology, 2015., 47(3), pp. 1001-8.
Koshiji, M., Kumamoto, K., Morimura, K., Utsumi, Y., Aizawa, M., Hoshino, M., Ohki, S., Takenoshita, S., Costa, M., Commes, T., Piquemal, D., Harris, C.C. & Tchou-Wong, K.M. Correlation of N-myc downstream-regulated gene 1 expression with clinical outcomes of colorectal cancer patients of different race/ethnicity. World journal of gastroenterology, 2007,13(20), pp. 2803-10.
Angst, E., Sibold, S., Tiffon, C., Weimann, R., Gloor, B., Candinas, D. & Stroka, D. Cellular differentiation determines the expression of the hypoxia- inducible protein NDRG1 in pancreatic cancer. British Journal of Cancer, 2006, 95(3), p. 307.
Sibold, S., Roh, V., Keogh, A., Studer, P., Tiffon, C., Angst, E., Vorburger, S.A., Weimann, R., Candinas, D. & Stroka, D. Hypoxia increases cytoplasmic expression of NDRG1, but is insufficient for its membrane localization in human hepatocellular carcinoma. FEBS letters, 2007, 581(5), pp. 989-94.
Gerhard, R., Nonogaki, S., Fregnani, J.H., Soares, F.A. & Nagai, M.A. NDRG1 protein overexpression in malignant thyroid neoplasms. Clinics (Sao Paulo, Brazil), 2010, 65(8), pp. 757-62.
Symes, A.J., Eilertsen, M., Millar, M., Nariculam, J., Freeman, A., Notara, M., Feneley, M.R., Patel, H.R., Masters, J.R. & Ahmed, Ax. Quantitative analysis of BTF3, HINT1, NDRG1 and ODC1 protein over-expression in human prostate cancer tissue. PLoS One, 2013, 8(12), p. e84295.
Song, Y., Oda, Y., Hori, M., Kuroiwa, K., Ono, M., Hosoi, F., Basaki, Y., Tokunaga, S., Kuwano, M., Naito, S. & Tsuneyoshi, M. N-myc downstream regulated gene-1/Cap43 may play an important role in malignant progression of prostate cancer, in its close association with E-cadherin. Human Pathology, 2010, 41(2), pp. 214-222.
Caruso, R.P., Levinson, B., Melamed, J., Wieczorek, R., Taneja, S., Polsky, D., Chang, C., Zeleniuch-Jacquotte, A., Salnikow, K., Yee, H., Costa, M. & Osman, I. Altered N-myc downstream-regulated gene 1 protein expression in African-American compared with caucasian prostate cancer patients. Clinical cancer research : an official journal of the American Association for Cancer Research, 2014, 10(1 Pt 1), pp. 222-7.
Bandyopadhyay, S., Pai, S.K., Gross, S.C., Hirota, S., Hosobe, S., Miura, K., Saito, K., Commes, T., Hayashi, S., Watabe, M. & Watabe, K. The Drg-1 gene suppresses tumor metastasis in prostate cancer. Cancer research, 2003, 63(8), pp. 1731-6.
Alghezi, D., Whitley, P., Beresford, M., Bowen, R., Mitchard, J. and Chalmers, A. Decreased ABCG2 expression in Prostate cancer and negatively asssociated with poorly differentiated grade and biochemical recurrence. Thi-Qar Medical Journal,. 2020, 20 (2), pp.243-256.
Hosoya, N., Sakumoto, M., Nakamura, Y., Narisawa, T., Bilim, V., Motoyama, T., Tomita, Y. & Kondo, T. Proteomics identified nuclear N- myc downstream- regulated gene 1 as a prognostic tissue biomarker candidate in renal cell carcinoma. BBA - Proteins and Proteomics, 2013, 1834(12), pp. 2630-2639.
Dalley, A.J.; Pitty, L.P.; Major, A.G.; Abdulmajeed, A.A. & Farah, C.S. Expression of ABCG 2 and B mi‐ 1 in oral potentially malignant lesions and oral squamous cell carcinoma. Cancer Medicine, 2014, 3(2), pp. 273-283.
Bae, D.-H., Jansson, P.J., Huang, M.L., Kovacevic, Z., Kalinowski, D., Lee, C.S., Sahni, S. & Richardson, D.R. The role of NDRG1 in the pathology and potential treatment of human cancers. J Clin Pathol, 2013, 66(11), p. 911
Jin, R., Liu, W., Menezes, S., Yue, F., Zheng, M., Kovacevic, Z. & Richardson, D.R. The metastasis suppressor NDRG1 modulates the phosphorylation and nuclear translocation of β- catenin through mechanisms involving FRAT1 and PAK4. Journal of cell science, 2014, 127(Pt 14), p. 3116
Kovacevic, Z., Chikhani, S., Lui, G.Y., Sivagurunathan, S. & Richardson, D.R. The iron-regulated metastasis suppressor NDRG1 targets NEDD4L, PTEN, and SMAD4 and inhibits the PI3K and Ras signaling pathways. Antioxidants & redox signaling, 2013, 18(8), pp. 874-87.
Wei, W., Bracher-Manecke, J.C., Zhao, X., Davies, N.H., Zhou, L., Ai, R., Oliver, L., Vallette, F. & Hendricks, D.T. Oncogenic but non-essential role of N-myc downstream regulated gene 1 in the progression of esophageal squamous cell carcinoma. Cancer biology & therapy, 2013, 14(2), pp. 164-74.
Ai, R., Sun, Y., Guo, Z., Wei, W., Zhou, L., Liu, F., Hendricks, D.T., Xu, Y. & Zhao, X. NDRG1 overexpression promotes the progression of esophageal squamous cell carcinoma through modulating Wnt signaling pathway. Cancer biology & therapy, 2016, 17(9), pp. 943-54.
