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

Abstract

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. IntroductionRenal cell carcinoma (RCC) is one of the leading causes of urological cancer-related mortality and clear cell renal cell carcinoma (ccRCC) is the most common type of RCC, accounting for 82% of RCC cases (1). Early-stage ccRCC is usually asymptomatic and difficult to accurately diagnose; in addition, ccRCC is resistant to conventional chemotherapeutic drugs and the overall clinical outcome is poor (2). The treatment of advanced ccRCC remains a major challenge for clinicians and ccRCC is responsible for ~35% of RCC-related mortality cases (1). Thus, there is an urgent need for diagnostic and prognostic biomarkers in ccRCC. However, there are currently no biomarkers for ccRCC in routine clinical practice. Over the last few years, prognostic markers for ccRCC, such as senescence-associated protein p400 (3), glyoxalase-1 (4), transforming growth factor-β-activated kinase-1 (5) and serum miR-210 (6), have emerged; however, their large-scale clinical application is not feasible. Therefore, novel diagnostic and prognostic markers of ccRCC would be valuable in high-risk individuals and in those with existing disease.Pituitary tumor-transforming gene-1 (PTTG1) was first isolated from rat pituitary tumor cells in 1997 and was identified as an oncogene, as PTTG1 overexpression was found to induce cellular transformation in vitro and tumor formation in nude mice (7). As a human securin, PTTG1 is involved in the mitotic spindle checkpoint pathway and inhibits sister chromatid separation to ensure chromosomal stability (7,8). In contrast to its restricted expression...

EZH2 cooperates with E2F1 to stimulate expression of genes involved in adrenocortical carcinoma aggressiveness

“…PTTG1 encodes Securin, a protein involved in the G2/M transition by inhibiting separation of sister chromatids 17 but also in DNA repair 18 and regulation of transcription. 19 It is a putative oncogene in a number of tissues such as the pituitary (where it was isolated) 20 and kidney 21 and was shown to be overexpressed in ACC by an independent study. 22 PRC1, also known as ASE1, encodes another key regulator of mitosis, which binds microtubules and is essential for the formation of the midzone bundle, central spindle organisation and subsequent cytokinesis.…”

“…PTTG1 encodes Securin, a protein involved in the G2/M transition by inhibiting separation of sister chromatids 17 but also in DNA repair 18 and regulation of transcription. 19 It is a putative oncogene in a number of tissues such as the pituitary (where it was isolated) 20 and kidney 21 and was shown to be overexpressed in ACC by an independent study. 22 …”

A Five-Gene Signature Predicts Prognosis in Patients with Kidney Renal Clear Cell Carcinoma

“…Many previous studies on genes in KIRC have mainly considered some known cancer-associated genes. For instance, Wei et al have found that high expression of pituitary tumor-transforming gene-1 ( PTTG1 ) in KIRC patients was associated with poor prognosis by using qRT-PCR and immunohistochemistry [ 27 ]. Peters et al have proved that low gene expression levels of GATA1 and GATA2 were related to tumor aggressiveness and short survival time in KIRC [ 28 ].…”

The long noncoding RNA urothelial carcinoma-associated 1 overexpression as a poor prognostic biomarker in clear cell renal cell carcinoma

“…34 ccRCC has a poor prognosis with the metastatic rate of 15.3%-21.5% at presentation and a 5-year cancer-specific survival rate of 55%-82.7%, due to late stage and resistance to chemoradiotherapy. [35][36][37][38][39][40] Previously, some genes have been identified to correlate with tumorigenicity and prognosis of ccRCC; however, there were conflicting reports. Recently, numerous evidence has shown the central role of lncRNA in the regulation of cell proliferation, differentiation, and apoptosis.…”