Abstract
Purpose
Up-regulated gene 4 (URG4) has been demonstrated to be involved in progression of various human cancers. This study investigated the clinicopathological significance of URG4 in epithelial ovarian cancer (EOC).
Methods
Immunohistochemistry was applied to investigate the expression of URG4 in ovarian tissues of 116 patients. The correlation of URG4 with proliferating cell nuclear antigen index (PCNA) was analyzed and the prognostic value of URG4 in patients was also investigated. Pearson Chi-square test, Spearman correlation coefficient, univariate analysis, multivariate analysis, and Kaplan–Meier method were adopted.
Results
The positive rate of URG4 in EOC was higher than that in borderline and benign tumors (P = 0.001). URG4 was positively correlated with PCNA (r = 0.86, P = 0.006). In addition, univariate analysis showed URG4 expression level, clinical stage, pathologic grade, lymphatic metastasis, chemotherapy, and ascites influenced survival time (all P < 0.05). In Cox multivariate analysis, all the aforementioned factors were found to be independent prognostic factors except pathologic grade and ascites (all P < 0.05).
Conclusions
Our results suggest for the first time that the URG4 might be involved in the progression of EOC. URG4 was a new target to assess the prognosis of EOC.
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References
Wang M, He Y, Shi L, Shi C (2011) Multivariate analysis by Cox proportional hazard model on prognosis of patient with epithelial ovarian cancer. Eur J Gynaecol Oncol 32:171–177
Pylvs M, Puistola U, Laatio L, Kauppila S, Karihtala P (2011) Elevated serum 8-OHdG is associated with poor prognosis in epithelial ovarian cancer. Anticancer Res 31:1411–1415
Yin M, Li C, Li X, Lou G, Miao B, Liu X, Meng F, Zhang H, Chen X, Sun M, Ling Q, Zhou R (2011) Over-expression of LAPTM4B is associated with poor prognosis and chemotherapy resistance in stages III and IV epithelial ovarian cancer. J Surg Oncol 104:29–36
Satiroglu-Tufan NL, Dodurga Y, Gok D, Cetinkaya A, Feitelson MA (2010) RNA interference-mediated URG4 gene silencing diminishes cyclin D1 mRNA expression in HepG2 cells. Genet Mol Res 9:1557–1567
Tufan NL, Lian Z, Liu J, Pan J, Arbuthnot P, Kew M, Clayton MM, Zhu M, Feitelson MA (2002) Hepatitis Bx antigen stimulates expression of a novel cellular gene, URG4, that promotes hepatocellular growth and survival. Neoplasia 4:355–368
Song J, Xie H, Lian Z, Yang G, Du R, Du Y, Zou X, Jin H, Gao J, Liu J, Fan D (2006) Enhanced cell survival of gastric cancer cells by a novel gene URG4. Neoplasia 8:995–1002
Huang J, Zhu B, Lu L, Lian Z, Wang Y, Yang X, Satiroglu-Tufan NL, Liu J, Luo Z (2009) The expression of novel gene URG4 in osteosarcoma: correlation with patients’ prognosis. Pathology 41:149–154
Wu X, Zhang Z, Cai S (1998) Proliferating cell nuclear antigen (PCNA) in ovarian carcinoma and its relation to lymph node metastasis and prognosis. Zhonghua Zhong Liu Za Zhi 20:68–70
Ciba Nurse P, Medal Lecture (1992) Eukaryotic cell-cycle control. Biochem Soc Trans 20:239–242
Vincent MD (2011) Cancer: beyond speciation. Adv Cancer Res 112:283–350
Baserga R, Porcu P, Sell C (1993) Oncogenes, growth factors and control of the cell cycle. Cancer Surv 16:201–213
Tong GD, Zhou DQ, He JS, Xiao CL, Liu XL, Zhou XZ, Zhang X, Xing YF, Lü P, Feitelson MA (2007) Preneoplastic markers of hepatitis B virus-associated hepatocellular carcinoma and their significance in clinical settings. Zhonghua Gan Zang Bing Za Zhi. 15:828–832
Fox JT, Lee KY, Myung K (2011) Dynamic regulation of PCNA ubiquitylation/deubiquitylation. FEBS Lett 585:2780–2785
Zhang W, Qin Z, Zhang X, Xiao W (2011) Roles of sequential ubiquitination of PCNA in DNA-damage tolerance. FEBS Lett 585:2786–2794
Abike F, Tapisiz OL, Zergeroglu S, Dunder I, Temizkan O, Payasli A (2011) PCNA and Ki-67 in endometrial hyperplasias and evaluation of the potential of malignancy. Eur J Gynaecol Oncol 32:77–80
Xu B, Hua J, Zhang Y, Jiang X, Zhang H, Ma T, Zheng W, Sun R, Shen W, Sha J, Cooke HJ, Shi Q (2011) Proliferating cell nuclear antigen (PCNA) regulates primordial follicle assembly by promoting apoptosis of oocytes in fetal and neonatal mouse ovaries. PLoS One 6:e16046
Sakuragi N, Yamada H, Oikawa M, Okuyama K, Fujino T, Sagawa T, Fujimoto S (2000) Prognostic significance of lymph node metastasis and clear cell histology in ovarian carcinoma limited to the pelvis (pT1M0 and pT2M0). Gynecol Oncol 79:251–255
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Li, W., Zhou, N. URG4 upregulation is associated with tumor growth and poor survival in epithelial ovarian cancer. Arch Gynecol Obstet 286, 209–215 (2012). https://doi.org/10.1007/s00404-012-2269-7
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DOI: https://doi.org/10.1007/s00404-012-2269-7