Abstract
BackgroundUpregulator of cell proliferation 4 (URG4) has been implicated in the oncogenesis of certain cancers. However, the correlation between URG4 expression and clinicopathological significance in human cancer remains unclear. Therefore, this study investigated its expression and clinicopathological significance in cervical cancer patients.MethodsURG4 expression was examined using quantitative PCR (qPCR) and western blotting in normal cervical epithelial cells, cervical cancer cells, and eight matched pairs of cervical cancer tissues and adjacent noncancerous tissues from the same patient. In addition, immunohistochemistry (IHC) was used to examine URG4 expression in paraffin-embedded tissues from 167 cervical cancer patients (FIGO stages Ib1-IIa2). Statistical analyses were performed to evaluate associations between URG4 expression and prognostic and diagnostic factors.ResultsURG4 was significantly upregulated in the cervical cancer cell lines and tissues compared with the normal cells and adjacent noncancerous cervical tissues. IHC revealed high URG4 expression in 59 out of the 167 (35.13%) cervical cancer specimens. Its expression was significantly correlated with clinical stage (P < 0.0001), tumour size (P = 0.012), T classification (P = 0.023), lymph node metastasis (P = 0.001) and vaginal involvement (P = 0.002). Patients with high URG4 expression, particularly those who received concurrent chemotherapy and radiotherapy (P < 0.0001), showed a shorter overall survival (OS) and disease-free survival (DFS) compared to those with the low expression of this protein. Multivariate analysis revealed that URG4 expression is an independent prognostic factor for cervical cancer patients.ConclusionsOur results demonstrated that elevated URG4 protein expression is associated with a poor outcome in patients with early-stage cervical cancer. URG4 may be a novel prognostic marker and therapeutic target for the treatment of cervical cancer.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-885) contains supplementary material, which is available to authorized users.
Highlights
Upregulator of cell proliferation 4 (URG4) has been implicated in the oncogenesis of certain cancers
Our results suggest that URG4 may be an independent biomarker for prognosis and that it represents a therapeutic target for the treatment of cervical cancer
The staining index was calculated as the product of the proportion of positive cells and the staining intensity score. Using this method of assessment, we evaluated URG4 expression in cervical cancer cells via a staining index (scored as 0, 1, Figure 1 Overexpression of URG4 mRNA and protein in cervical cancer cell lines. Expression levels of URG4 mRNA and protein in cervical cancer cell lines (HeLa, HeLa 229, hepatocellular carcinoma (HCC) 94, C33a, Ca Ski, MS751, ME-180 and SiHa) and normal cervical cell lines were examined via western blotting (a) and quantitative PCR (qPCR) (b)
Summary
Upregulator of cell proliferation 4 (URG4) has been implicated in the oncogenesis of certain cancers. Traditional pathological variables are not sufficiently reliable for predicting clinical outcomes or for guiding optimal treatment strategies Many genes, such as annexin A2, Sam and HDAC10 [5,6,7], have been reported to be potentially useful prognostic markers in cervical cancer, but there is still an urgent need for additional research to identify novel biomarkers to supply practical information for patient prognosis and suitable therapeutic options. Upregulated gene 4 (URG4) has been identified as an oncogene with a full-length mRNA of 3.607 kb that encodes a protein of approximately 104 kDa in size This gene may be associated with the onset of oncogenesis and cell cycle regulation [8,9,10]. The clinical significance of this gene in human cervical cancer remains unknown
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