Abstract
The present study was conducted to investigate the clinical significance of cAMP responsive element binding protein 3 like 1 (CREB3L1) and pleiotrophin (PTN) expression in prognosis of patients with brain gliomas. Human brain tissue samples were collected from normal glial tissues (control), low- and high-grade glioma tissues. CREB3L1 and PTN expression levels in cells were assessed by immunohistochemistry (IHC), and population distribution of the CREB3L1- and PTN-presenting patients was examined. The CREB3L1 and PTN mRNA expression levels in three types of the brain cells was determined by RT-PCR. Survival rates for population of the CREB3L1- and PTN-presenting patients were examined. CREB3L1+ cell counts were decreased with increased PTN+ cells in the low-grade and high-grade glioma tissues as compared with the control. Population proportion of the CREB3L1+-presenting patients decreased from the control to the high-grade glioma and the population of the PTN+-presenting patients increased in low- and high-grade gliomas as compared with the control (both P<0.05). The decrease in the CREB3L1 mRNA expression was associated with the increase in the PTN mRNA expression in the low- and high-grade gliomas (P<0.05). Survival time for patients with CREB3L1− and PTN+ gliomas was shorter than patients with CREB3L1+ and PTN− gliomas in the investigated cohorts (both P<0.05). There was a relationship between the expression levels of both proteins and survival time. CREB3L1 and PTN expression levels serve as biomarkers with utility in grading gliomas. Absence of CREB3L1 and presence of PTN in brain glioma cells correlate with survival time of the glioma patients.
Highlights
Most tumors in the brain are gliomas originating in the glial cells and are often diagnosed as malignant brain tumors [1]
It has been reported that loss of CREB3L1 expression may contribute to or be required for cancer progression and the development of a metastatic phenotype [8,16,17]
PTN expression is increased in a number of human cancers, in particular brain tumors [11,18] and is thought to be involved in tumor angiogenesis [19]
Summary
Most tumors in the brain are gliomas originating in the glial cells and are often diagnosed as malignant brain tumors [1]. Gliomas can be life-threatening depending on the grade of malignancy. Grades III and IV are the highest grades based on tumor’s growth potential and aggressiveness, with the worst prognosis and greatest need for the most aggressive treatment [2-4]. The exact cause of glioma is not known and patients have a median life expectancy following diagnosis and aggressive treatment of just 14 months [5]. CREB3L1 expression is frequently altered in many cancer types suggesting that it could have a broader role in cancer progression and metastasis [7,8]. Pleiotrophin (PTN) is an angiogenic and mitogenic growth factor for various cell types and produced by some human tumors [9,10]. The tumor-secreted PTN is supposed to contribute to tumor’s malignancy by targetting endothelial and microglial cells [11]
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