High expression of pituitary tumor-transforming gene-1 predicts poor prognosis in clear cell renal cell carcinoma

Wei,Can; Yang,Xiaoliang; Xi,Junhua; Wu,Wei; Yang,Zhenxing; Wang,Wei; Tang,Zhiguo; Ying,Quansheng; Zhang,Yanbin

doi:10.3892/mco.2014.478

High expression of pituitary tumor-transforming gene-1 predicts poor prognosis in clear cell renal cell carcinoma

Authors:
- Can Wei
- Xiaoliang Yang
- Junhua Xi
- Wei Wu
- Zhenxing Yang
- Wei Wang
- Zhiguo Tang
- Quansheng Ying
- Yanbin Zhang
View Affiliations

Affiliations: Department of Urology, Hefei Hospital Affiliated to Anhui Medical University/The Second People's Hospital of Hefei, Hefei, Anhui 230011, P.R. China
Published online on: December 18, 2014 https://doi.org/10.3892/mco.2014.478
Pages: 387-391

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Pituitary tumor‑transforming gene‑1 (PTTG1) is a recently identified oncogene involved in the progression of malignant tumors; however, the expression level of PTTG1 in clear cell renal cell carcinoma (ccRCC) and its potential value as a novel prognostic marker for ccRCC remains unclear. In this study, PTTG1 mRNA and protein levels were assessed in 44 paired ccRCC tissues and adjacent normal tissues by quantitative polymerase chain reaction (qPCR) and immunohistochemistry, respectively. further immunohistochemical analysis was implemented in 192 samples of ccRCC to evaluate the associations between PTTG1 levels and the clinical characteristics in ccRCC. Reverse transcription qPCR and immunohistochemical analysis demonstrated that the PTTG1 mRNA and protein levels were significantly higher in ccRCC compared to normal tissues. In addition, the PTTG1 protein level in 192 ccRCC samples was found to be significantly correlated with T stage, N classification, metastasis, recurrence and Fuhrman grade, whereas it was not associated with age and gender. Patients with low PTTG1 levels exhibited a better survival outcome compared to those with a higher PTTG1 level. PTTG1 expression and N stage were identified as independent prognostic factors for the overall survival of ccRCC patients. The results suggested that the overexpression of PTTG1 indicates a poor prognosis in ccRCC patients and, therefore, PTTG1 may serve as a novel prognostic marker for ccRCC.

View Figures

View References

1	Siegel R, Ma J, Zou Z and Jemal A: Cancer statistics, 2014. CA Cancer J Clin. 64:9–29. 2014. View Article : Google Scholar : PubMed/NCBI
2	Singer EA, Gupta GN, Marchalik D and Srinivasan R: Evolving therapeutic targets in renal cell carcinoma. Curr Opin Oncol. 25:273–280. 2013.PubMed/NCBI
3	Macher-Goeppinger S, Bermejo JL, Schirmacher P, Pahernik S, Hohenfellner M and Roth W: Senescence-associated protein p 400 is a prognostic marker in renal cell carcinoma. Oncol Rep. 30:2245–2253. 2013.PubMed/NCBI
4	Tanaka T, Kuramitsu Y, Wang Y, et al: Glyoxalase 1 as a candidate for indicating the metastatic potential of SN12C human renal cell carcinoma cell clones. Oncol Rep. 30:2365–2370. 2013.PubMed/NCBI
5	Wei C, Lai YQ, Li XX and Ye JX: TGF-β-activated kinase-1: a potential prognostic marker for clear cell renal cell carcinoma. Asian Pac J Cancer Prev. 14:315–320. 2013. View Article : Google Scholar : PubMed/NCBI
6	Iwamoto H, Kanda Y, Sejima T, Osaki M, Okada F and Takenaka A: Serum miR-210 as a potential biomarker of early clear cell renal cell carcinoma. Int J Oncol. 44:53–58. 2014.PubMed/NCBI
7	Pei L and Melmed S: Isolation and characterization of a pituitary tumor-transforming gene (PTTG). Mol Endocrinol. 11:433–441. 1997. View Article : Google Scholar : PubMed/NCBI
8	Zou H, McGarry TJ, Bernal T and Kirschner MW: Identification of a vertebrate sister-chromatid separation inhibitor involved in transformation and tumorigenesis. Science. 285:418–422. 1999. View Article : Google Scholar : PubMed/NCBI
9	Feng ZZ, Chen JW, Yang ZR, Lu GZ and Cai ZG: Expression of PTTG1 and PTEN in endometrial carcinoma: correlation with tumorigenesis and progression. Med Oncol. 29:304–310. 2012. View Article : Google Scholar : PubMed/NCBI
10	Yoon CH, Kim MJ, Lee H, et al: PTTG1 oncogene promotes tumor malignancy via epithelial to mesenchymal transition and expansion of cancer stem cell population. J Biol Chem. 287:19516–19527. 2012. View Article : Google Scholar : PubMed/NCBI
11	Fuhrman SA, Lasky LC and Limas C: Prognostic significance of morphologic parameters in renal cell carcinoma. Am J Surg Pathol. 6:655–663. 1982. View Article : Google Scholar : PubMed/NCBI
12	Wei C, Wu S, Li X, Wang Y, Ren R, Lai Y and Ye J: High expression of FER tyrosine kinase predicts poor prognosis in clear cell renal cell carcinoma. Oncol Lett. 5:473–478. 2013.PubMed/NCBI
13	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2–ΔΔCt method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
14	Demeure MJ, Coan KE, Grant CS, et al: PTTG1 overexpression in adrenocortical cancer is associated with poor survival and represents a potential therapeutic target. Surgery. 154:1405–1416. 2013. View Article : Google Scholar : PubMed/NCBI
15	Kakar SS and Jennes L: Molecular cloning and characterization of the tumor transforming gene (TUTR1): a novel gene in human tumorigenesis. Cytogenet Cell Genet. 84:211–216. 1999. View Article : Google Scholar : PubMed/NCBI
16	Hamid T, Malik MT and Kakar SS: Ectopic expression of PTTG1/securin promotes tumorigenesis in human embryonic kidney cells. Mol Cancer. 4:32005. View Article : Google Scholar : PubMed/NCBI
17	Huang SQ, Liao QJ, Wang XW, Xin DQ, Chen SX, Wu QJ and Ye G: RNAi-mediated knockdown of pituitary tumor-transforming gene-1 (PTTG1) suppresses the proliferation and invasive potential of PC3 human prostate cancer cells. Braz J Med Biol Res. 45:995–1001. 2012. View Article : Google Scholar : PubMed/NCBI
18	Caporali S, Alvino E, Levati L, et al: Down-regulation of the PTTG1 proto-oncogene contributes to the melanoma suppressive effects of the cyclin-dependent kinase inhibitor PHA-848125. Biochem Pharmacol. 84:598–611. 2012. View Article : Google Scholar : PubMed/NCBI
19	Solbach C, Roller M, Peters S, Nicoletti M, Kaufmann M and Knecht R: Pituitary tumor-transforming gene (PTTG): a novel target for anti-tumor therapy. Anticancer Res. 25:121–125. 2005.PubMed/NCBI
20	Cho-Rok J, Yoo J, Jang YJ, et al: Adenovirus-mediated transfer of siRNA against PTTG1 inhibits liver cancer cell growth in vitro and in vivo. Hepatology. 43:1042–1052. 2006. View Article : Google Scholar : PubMed/NCBI
21	Hsu YH, Liao LJ, Yu CH, et al: Overexpression of the pituitary tumor transforming gene induces p 53-dependent senescence through activating DNA damage response pathway in normal human fibroblasts. J Biol Chem. 285:22630–22638. 2010. View Article : Google Scholar : PubMed/NCBI
22	Bernal JA, Luna R, Espina A, et al: Human securin interacts with p 53 and modulates p 53-mediated transcriptional activity and apoptosis. Nat Genet. 32:306–311. 2002. View Article : Google Scholar : PubMed/NCBI
23	Liang M, Chen X, Liu W, Li S, Li C, Jiang L and Lv S: Role of the pituitary tumor transforming gene 1 in the progression of hepatocellular carcinoma. Cancer Biol Ther. 11:337–345. 2011. View Article : Google Scholar : PubMed/NCBI
24	Levi F, Ferlay J, Galeone C, Lucchini F, Negri E, Boyle P and La Vecchia C: The changing pattern of kidney cancer incidence and mortality in Europe. BJU Int. 101:949–958. 2008. View Article : Google Scholar : PubMed/NCBI