Abstract
AimThe aberrant expression of regenerating islet-derived family member, 4 (Reg IV) has been found in various human cancers. However, the roles of Reg IV gene and its encoding product in human glioma have not been clearly understood. Therefore, the aim of this study was to investigate the clinicopathological significance of Reg IV expression in glioma.MethodsReg IV mRNA and protein expression in human gliomas and non-neoplastic brain tissues were respectively detected by real-time quantitative RT-PCR assay, Western blot, and immunohistochemistry. The association of Reg IV immunostaining with clinicopathological factors and prognosis of glioma patients was also statistically analyzed.ResultsReg IV mRNA and protein expression levels in glioma tissues were both significantly higher than those in the corresponding non-neoplastic brain tissues (both P < 0.001). Additionally, the increased Reg IV immunostaining in glioma tissues was significantly associated with advanced pathological grade (P = 0.008). Reg IV protein up-regulation was also significantly correlated with low Karnofsky performance score (KPS) (P = 0.02). Moreover, the overall survival of patients with high Reg IV protein expression was dramatically shorter than those with low Reg IV protein expression (P < 0.001). Multivariate Cox regression analysis further confirmed that Reg IV expression was an independent prognostic factor for patients with gliomas (P = 0.008).ConclusionsThese convinced evidences suggest for the first time that Reg IV might accelerate disease progression and act as a candidate prognostic marker for gliomas.Virtual slidesThe virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/2145344361720706
Highlights
Human glioma represents the most common malignancy in central nervous system for both children and adults
Reg IV mRNA and protein expression in human glioma tissues The expression levels of Reg IV mRNA were detected in 20 glioma and 10 non-neoplastic brain tissues normalized to glyceraldehyde 3-phosphate dehydrogenase (GAPDH)
The statistic results showed that its expression in high-grade (III: 2.4 ± 0.1; IV: 2.0 ± 0.09) and low-grade (I: 1.5 ± 0.03; II: 1.7 ± 0.07) gliomas were both significantly higher than that in non-neoplastic brains tissues (0.8 ± 0.03; Grade I vs. N: P = 0.003; Grade II vs. N: P = 0.003; Grade III vs. N: P < 0.001; Grade IV vs. N: P < 0.001; Figure 1C)
Summary
Human glioma represents the most common malignancy in central nervous system for both children and adults. As the most recently discovered member of the human Reg family proteins, Reg IV has been demonstrated to enhance cell proliferation and inhibit apoptosis by inducing phosphorylation of epidermal growth factor receptor (EGFR) (Tyr992, Tyr1068) and Akt (Thr308, Ser473) [7]. The expression of Reg IV mRNA is restricted to gastrointestinal tract, pancreas, prostate, and testes [8]. The role of Reg IV gene and its encoding product in human glioma has not been clearly understood. To address this problem, Reg IV expression at mRNA and protein levels in human glioma and non-neoplastic brain tissues were respectively measured by real-time quantitative RT-PCR assay, Western blot, and immunohistochemistry. The association of Reg IV immunostaining with clinicopathological factors or prognosis of glioma patients was statistically analyzed
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