Abstract
Recent experimental evidence support the model in which the simultaneous induction of BMI-1 and USP22 is critical during cancer progression. Whether this model may affect gastric cancer (GC) progression is worthy of additional study. In this study, we examined the significance of the USP22 and BMI-1 expression in GC (n = 219), non-cancerous mucosa (n = 37), and lymph node metastasis (n = 37). The protein expression level of USP22 and BMI-1 were concomitantly up-regulated from non-cancerous mucosa to primary carcinoma and from carcinomas to lymph node metastasis (P < 0.001). A statistical correlation was observed between USP22 and BMI-1 expression in GC tissues (n = 219, r = 0.634, P < 0.001) and in lymph node metastasis (n = 37, r = 0.689, P < 0.001). The incidence of positive expression was 57.08% for USP22, 49.32% for BMI-1, and 45.21% for USP22/BMI-1 in 219 GC tissues, respectively. Co-positive of USP22/BMI-1 was significantly correlated with gross features (x 2 = 14.256, P < 0.001), differentiation (x 2 = 5.872, P = 0.015), pT classification (x 2 = 18.486, P < 0.001), pN classification (x 2 = 9.604, P = 0.002), pM classification (x 2 = 32.766, P < 0.001), and AJCC stage (x 2 = 58.278, P < 0.001). Notably, high USP22/BMI-1 expression was significantly associated with shorter disease-specific survival (P < 0.001). By Cox regression analysis, co-positive of USP22/BMI-1 was found to be an independent prognostic factor (P = 0.002). Our results indicated the simultaneous activation of USP22 and BMI-1 may associate with GC progression and therapy failure.
Similar content being viewed by others
References
Glinsky, G. V. (2005). Death-from-cancer signatures and contribution of stem cells to metastatic cancer. Cell Cycle, 4, 1171–1175.
Glinsky, G. V., Berezovska, O., & Glinskii, A. B. (2005). Microarray analysis identifies a death from cancer signature predicting therapy failure in patients with multiple types of cancer. Journal of Clinical Investigation, 115, 1503–1521.
Glinsky, G. V. (2006). Integration of HapMap-based SNP pattern analysis and gene expression profiling reveals common SNP profiles for cancer therapy outcome predictor genes. Cell Cycle, 5, 2613–2625.
Glinsky, G. V. (2008). “Stemness” genomics law governs clinical behavior of human cancer: implications for decision making in disease management. Journal of Clinical Oncology, 26, 2846–2853.
Glinsky, G. V. (2006). Genomic models of metastatic cancer: functional analysis of death-from-cancer signature genes reveals aneuploid, anoikis-resistant, metastasis-enabling phenotype with altered cell cycle control and activated Polycomb Group (PcG) protein chromatin silencing pathway. Cell Cycle, 5, 1208–1216.
Liu, S., Dontu, G., Mantle, I. D., Patel, S., Ahn, N. S., Jackson, K. W., et al. (2006). Hedgehog signaling and bmi-1 regulate self-renewal of normal and malignant human mammary stem cell. Cancer Research, 66, 6063–6071.
Park, I. K., Qian, D., Kiel, M., Becker, M. W., Pihalja, M., Weissman, I. L., et al. (2003). Bmi-1 is required for maintenance of adult self-renewing haematopoietic stem cells. Nature, 423, 302–305.
Molofsky, A. V., Pardal, R., Iwashita, T., Park, I. K., Clarke, M. F., & Morrison, S. J. (2003). Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation. Nature, 425, 962–967.
Lessard, J., & Sauvageau, G. (2003). Bmi-1 determines the proliferative capacity of normal and leukaemic stem cells. Nature, 423, 255–260.
Berezovska, O. P. (2006). Essential role for activation of the Polycomb group (PcG) protein chromatin silencing pathway in metastatic prostate cancer. Cell Cycle, 5, 1886–1901.
Lee, H. J., Kim, M. S., Shin, J. M., Park, T. J., Chung, H. M., & Baek, K. H. (2006). The expression patterns of deubiquitinating enzymes, USP22 and Usp22. Gene Expression Patterns, 6, 277–284.
Zhang, X. Y., Pfeiffer, H. K., Thorne, A. W., & McMahon, S. B. (2008). USP22, an hSAGA subunit and potential cancer stem cell marker, reverses the polycomb-catalyzed ubiquitylation of histone H2A. Cell Cycle, 7, 1522–1524.
Zhang, X. Y., Varthi, M., Sykes, S. M., Phillips, C., Warzecha, C., Zhu, W., et al. (2008). The putative cancer stem cell marker USP22 is a subunit of the human SAGA complex required for activated transcription and cell-cycle progression. Molecular Cell, 29, 102–111.
Zhao, Y., Lang, G., Ito, S., Bonnet, J., Metzger, E., Sawatsubashi, S., et al. (2008). A TFTC/STAGA module mediates histone H2A and H2B deubiquitination, coactivates nuclear receptors, and counteracts heterochromatin silencing. Molecular Cell, 29, 92–101.
Pijnappel, W. W., & Timmers, H. T. (2008). Dubbing SAGA unveils new epigenetic crosstalk. Molecular Cell, 29, 152–154.
Yu, Q., Su, B., Liu, D., Liu, B., Fan, Y., Wang, Y., et al. (2007). Antisense RNA-mediated suppression of Bmi-1 gene expression inhibits the proliferation of lung cancer cell line A549. Oligonucleotides, 17, 327–335.
Jacobs, J. J., Kieboom, K., Marino, S., DePinho, R. A., & van Lohuizen, M. (1999). The oncogene and Polycomb-group gene bmi-1 regulates cell proliferation and senescence through the INK4A locus. Nature, 397, 164–168.
Haupt, Y., Alexander, W. S., Barri, G., Klinken, S. P., & Adams, J. M. (1991). Novel zinc finger gene implicated as myc collaborator by retrovirally accelerated lymphomagenesis in E mu-myc transgenic mice. Cell, 65, 753–763.
Schwartz, Y. B., & Pirrotta, V. (2007). Polycomb silencing mechanisms and the management of genomic programmes. Nature Reviews. Genetics, 8, 9–22.
Silva, J., García, J. M., Peña, C., García, V., Domínguez, G., Suárez, D., et al. (2006). Implication of polycomb members Bmi-1, Mel-18, and Hpc-2 in the Regulation of p16INK4a, p14ARF, h-TERT, and c-Myc expression in primary breast carcinomas. Clinical Cancer Research, 12, 6929–6936.
Liu, Y. L., Yang, Y. M., Xu, H., & Dong, X. S. (2010). Increased expression of ubiquitin-specific protease 22 can promote cancer progression and predict therapy failure in human colorectal cancer. Journal of Gastroenterology and Hepatology, 25, 1800–1805.
Glinsky, G. V. (2007). Stem cell origin of death-from-cancer phenotypes of human prostate and breast cancers. Stem Cell Reviews, 3, 79–93.
Henry, K. W., Wyce, A., Lo, W. S., Duggan, L. J., Emre, N. C., Kao, C. F., et al. (2003). Transcriptional activation via sequential histone H2B ubiquitylation and deubiquitylation, mediated by SAGA-associated Ubp8. Genes and Development, 17, 2648–2663.
Wang, H., Wang, L., Erdjument-Bromage, H., Vidal, M., Tempst, P., Jones, R. S., et al. (2004). Role of histone H2A ubiquitination in Polycomb silencing. Nature, 431, 873–878.
Acknowledgments
This work was supported by Natural Science Foundation of Heilongjiang Province (ZD200920). This work was also supported by grant of Harbin Science and Technology Bureau (2007AA3CS083).
Author information
Authors and Affiliations
Corresponding author
Additional information
Dong-Dong Yang and Bin-Bin Cui contributed equally to this work.
Rights and permissions
About this article
Cite this article
Yang, DD., Cui, BB., Sun, Ly. et al. The Co-expression of USP22 and BMI-1 May Promote Cancer Progression and Predict Therapy Failure in Gastric Carcinoma. Cell Biochem Biophys 61, 703–710 (2011). https://doi.org/10.1007/s12013-011-9229-x
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12013-011-9229-x