Abstract
Protein tyrosine phosphatase 4A2 (PTP4A2) has been implicated as an oncogenic protein in several human cancers. However, the level of PTP4A2 expression and its prognostic significance in nasopharyngeal carcinoma (NPC) remains unknown. In this study, Western blotting (WB), quantitative real-time PCR (qT-PCR) and immunohischemistry (IHC) was applied to evaluated the expression levels of PTP4A2 in NPC cell lines and tumor tissues combining two independent cohorts. Receiver-operator curve (ROC) analysis was used to assessed the optimal cut-off score in training cohort (266 cases). This cut-off score was subjected to determine the association of PTP4A2 expression with patients’ clinical characteristics and survival outcome in the validation cohort (201 cases) and the overall population (467 cases). We found that PTP4A2 were significantly overexpressed in NPC cell lines compared with normal nasopharyngeal epithelial cell. Moreover, overexpression of PTP4A2 was positively correlated with advanced T classification (P<0.001) and TNM stages (P<0.001). And higher PTP4A2 expression was an independent prognostic factor for adverse overall survival (P<0.05) and poor disease-free survival (P<0.05). Our results demonstrated that the overexpression of PTP4A2 was closely associated with poor survival outcome in patients with NPC and may represent a novel prognostic biomarker and therapeutic target for this disease.
Highlights
Nasopharyngeal carcinoma (NPC), an Epstein-Bar virus (EBV)-related head and neck cancer, is a neoplastic disorder that arises from the epithelial lining of the nasopharynx [1]
Western blotting and quantitative real-time PCR was applied to analysis the expression levels of Protein tyrosine phosphatase 4A2 (PTP4A2) protein and mRNA in five nasopharyngeal carcinoma (NPC) cell lines (CNE1, CNE2, C666, HONE1 and SUNE1) and one immortalized primary nasopharyngeal epithelial cell line (NPEC2 Bmi-1)
Our western blotting analysis demonstrated that NPC cell lines exhibited higher level of PTP4A2 protein expression as compared to that in NPEC2 Bmi-1 (Figure 1A: left). Quantitative real-time polymerase chain reaction (qRT-PCR) revealed elevated expression of PTP4A2 mRNA in CNE1, CNE2, C666, HONE1 and SUNE1 compared to NPEC2 Bmi-1 (Figure 1A: right)
Summary
Nasopharyngeal carcinoma (NPC), an Epstein-Bar virus (EBV)-related head and neck cancer, is a neoplastic disorder that arises from the epithelial lining of the nasopharynx [1]. Accumulating evidence supported that enhanced expression of members of the human phosphatase of regenerating liver(PRL) subgroup of PTPs is linked to the progression of human cancer. This family are encoded by the PTP4A1, PTP4A2, and PTP4P3 genes, respectively [6, 7]. Previous studies have showed that up-regulation of the PRLs, especially PTP4A1 and PTP4A3 could promote cell invasion, migration and metastasis during tumor development and progression [8,9,10]. Few studies have reported the specific functions of PTP4A2 in human cancer types. We reported previously PTP4A2 was up-regulated in colorectal cancer (CRC) and associated with CRC metastasis [11]. To the best of our knowledge, the expression pattern of PTP4A2 and its clinical significance in NPC remains inconclusive
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