Prognostic Factor In Glioma Research Articles

Low LINC00599 expression is a poor prognostic factor in glioma.

LINC00599 has been suggested to be involved in physiological and pathological processes including carcinogenesis. However, the clinical and prognostic significance of LINC00599 in glioma patients and the effect of LINC00599 on glioma cell migration and invasion remain unknown. In our results, we first observe the expression of LINC00599 in 31 types of human cancers including tumor tissues and corresponding normal tissues at The Cancer Genome Atlas (TCGA) database, and found that LINC00599 expression levels were only reduced in lower grade glioma (LGG) tissues and glioblastoma multiforme (GBM) tissues compared with normal brain tissues. Moreover, we confirmed levels of LINC00599 expression were decreased in glioma tissues and cell lines compared with matched adjacent normal tissues and normal human astrocytes (NHAs), respectively. Meanwhile, we found that glioma tissues with WHO III-IV grade exhibited lower levels of LINC00599 expression than glioma tissues with I-II grade. The survival analysis at TCGA data showed low LINC00599 expression was associated with poor disease-free survival and overall survival in glioma patients. In vitro study suggested up-regulation of LINC00599 depressed glioma cell migration and invasion through regulating epithelial–mesenchymal transition (EMT) process. In conclusion, LINC00599 acts as a tumor-suppressing long non-coding RNA (lncRNA) in glioma.

Peripheral blood test provides a practical method for glioma evaluation and prognosis prediction.

SummaryObjectiveTo investigate the relationship between tumor characteristics and the preoperative counts of immune cells in peripheral blood test in glioma patients.MethodsWe included 260 WHO grades II‐IV patients who had preoperative peripheral blood test result from Sanbo hospital as training set. The 66 patients from Tiantan hospital was obtained for validation. RNA sequencing data from CGGA and TCGA datasets were used to evaluate the features of neutrophil subtype and lymphocyte subtype in glioma.ResultsWe revealed that the count of preoperative lymphocytes, eosinophils and neutrophils were associated with glioma grades. Neutrophil‐to‐lymphocyte ratio (NLR) <3.2 was associated with better prognosis, whereas increased NLR was strongly corresponding with a poor prognosis. Lymphocyte type glioma patients demonstrated a positive correlation with isocitrate dehydrogenase (IDH) mutation and lower grade. IDH mutant glioma contained a higher proportion of tumor‐infiltrating lymphocytes than IDH wild‐type glioma. The immune subtype (neutrophil subtype and lymphocyte subtype) was an independent prognostic factor in glioma.ConclusionOur data demonstrated that NLR was an important prognostic factor in glioma. We classified that the immune subtype of glioma may contribute to a better understanding of disease pathogenesis and lead to the identification of new therapeutic targets for glioma patients.

REST, not REST4, is a risk factor associated with radiotherapy plus chemotherapy efficacy in glioma.

Background/aimRepressor element silencing transcription factor (REST) is a transcription repressor, expressed in several malignancies. This study aims to evaluate the prognostic values of REST and its splicing variant REST4 in glioma, and investigate the potential correlation between REST and REST4.MethodsREST and REST4 expression values were evaluated by qRT-PCR in 89 patients with gliomas and 10 with normal brain tissues.ResultsUpregulation of REST was related to higher World Health Organization (WHO) grade, larger tumor size, higher ki67, and higher p53 positive rate. After radiotherapy+temozolomide (RT+TMZ) treatment, low REST expression patients could get better therapeutic efficacy (P=0.031). The positive rate of REST4 expression was only 13.5% in glioma tissues, and REST4 expression was not associated with clinical characteristics and REST expression in this study.ConclusionsREST was a prognostic factor in glioma, while REST4 was not. REST expression can be a predictor in evaluating the survival outcome of gliomas patients treated with RT+TMZ after surgery.

Contrast enhancement predicting survival in integrated molecular subtypes of diffuse glioma: an observational cohort study

To assess the predictive value of magnetic resonance imaging (MRI) gadolinium enhancement as a prognostic factor in the 2016 World Health Organization Classification of Tumors of the Central Nervous System integrated glioma groups. Four-hundred fifty patients with histopathologically confirmed glioma were retrospectively assessed between 07/1997 and 06/2014 using gadolinium enhancement, survival, and relevant prognostic molecular data [isocitrate dehydrogenase (IDH); alpha-thalassemia/mental retardation syndrome X-linked (ATRX); chromosome 1p/19q loss of heterozygosity; and O6-methylguanine DNA methyltransferase (MGMT)]. The Kaplan-Meier method was used to assess univariate survival data. A multivariate Cox proportional hazards model was performed on significant results from the univariate analysis. There were significant differences in survival between patient age (p < 0.0001), WHO glioma grades (p < 0.0001), and integrated molecular profiles (p < 0.0001). Patients with IDH1/2 mutation, loss of ATRX expression, and methylated MGMT promoter showed significantly better survival than those with the IDHwild-type (p < 0.0001), retained ATRX expression (p < 0.0001), and unmethylated MGMT promoter (p = 0.019). Survival was significantly better in patients without gadolinium enhancement (p = 0.009) who were in the IDHwild-type glioma and glioma with retained ATRX expression groups (p = 0.018 and 0.030, respectively). In univariate analysis, the presence of gadolinium enhancement on preoperative MRI scans is an unfavorable factor for survival. Regarding the molecular subgroups, gadolinium enhancement is an unfavorable prognostic factor in gliomas with IDHwild-type and those with ATRX retention. However, in multivariate analysis only patient age, IDH1/2 mutation status, MGMT promoter methylation status, and WHO grade IV are relevant for predicting survival.

MiR-205 enhances cisplatin sensitivity of glioma cells by targeting E2F1.

miR-205 has been previously identified as a diagnostic and prognostic factor in glioma. However, its exact functions in glioma remain unclear. The current research aimed to decipher the role of miR-205 in the development of cisplatin resistance in glioma cells. miR-205 expressions in both cisplatin sensitive and resistant cell lines were compared by the Real-time PCR method. The dose-response to cisplatin of U87/DDP cells was determined by MTT assay. Cell cycle and apoptosis were determined by flow cytometry, caspase 3/7 activity assay and Western blot assay. The direct repression of E2F1 by miR-205 was confirmed by luciferase assay and Western blot assay. miR-205 expression was decreased in cisplatin resistant glioma cell lines, and cisplatin treatment led to a decrease of miR-205 in glioma cells. Overexpression of miR-205 in U87/DDP restored its cisplatin sensitivity by enhancing apoptosis and G1/S cell cycle arrest; notably, all these effects were then partially abrogated by E2F1 overexpression. Luciferase assay and Western blot assay confirmed E2F1 as the direct target of miR-205 in U87/DDP cells. These findings suggest that down-regulation of miR-205 confers the cisplatin resistance in glioma cells via upregulation of E2F1. It might serve as a candidate for glioma therapy.

BRAF Mutation is Associated with an Improved Survival in Glioma-a Systematic Review and Meta-analysis.

Newly emerged molecular markers in gliomas provide prognostic values beyond the capabilities of histologic classification. BRAF mutation, especially BRAF V600E, is common in a subset of gliomas and may represent a potential prognostic marker. The aim of our study is to investigate the potential use of BRAF mutations on prognosis of glioma patients. Four electronic databases were searched for potential articles, including PubMed, Scopus, ISI Web of Science, and Virtual Health Library (VHL). Data of hazard ratio (HR) for overall survival (OS) and progression-free survival (PFS) were directly obtained from original papers or indirectly estimated from Kaplan Meier curve (KMC). A random effect model weighted by inverse variance method was used to calculate the pooled HR. From 705 articles, we finally included 11 articles with 1308 glioma patients for the final analysis. The overall estimates showed that BRAF V600E was associated with an improved overall survival (OS) in glioma patients (HR=0.60; 95% CI=0.44-0.80). Results for progression-free survival (PFS), however, were not statistically significant (HR=1.39; 95% CI=0.82-2.34). In subgroup analyses, BRAF V600E showed its effect in improving survival in pediatric and young adult gliomas (under 35years) but did not have prognostic value in old adult. Additionally, BRAF V600E was only associated with a favorable prognosis in lower grade glioma. Our meta-analysis provides evidence that BRAF mutation has a favorable prognostic impact in gliomas and its prognostic value might be dependent on patient age and tumor grade. This mutation can be used as a prognostic factor in glioma but additional studies are required to clarify its prognostic value taking into account other confounding factors.

Gpx 4 is involved in the proliferation, migration and apoptosis of glioma cells

Glioma is one of the most common and aggressive types of human brain tumor, it is important to explore novel glioma-associated genes. In this report, we defined Gpx4 as a therapeutic target for glioma. Western blot and immunohistochemistry(IHC) analysis revealed that the protein level of Gpx4 was higher in glioma tissues and cell lines. In addition, IHC stain revealed that there was statistical significance between the expression of Gpx4 and the WHO grade (P=0.004) and Ki-67(P=0.000) expression. Kaplan–Meier curve showed that high expression of Gpx4 was associated with poor prognosis of glioma patients (P<0.01). To determine whether Gpx4 could regulate the proliferation and migration of glioma cells, we transfected glioma cells with Gpx4-siRNA and then investigated cell proliferation with cell counting kit (CCK) −8, flow cytometry assay and colony formation analyses, and we used wound-healing and transwell assays to investigate cell migration. Our results indicated that knockdown of Gpx4 would inhibit the proliferation and migration of glioma cells. Besides, silencing of Gpx4 could induce the apoptosis of glioma cells. This research indicated that Gpx4 might be thought of as a new prognostic factor in glioma and be closely correlated with glioma cell proliferation, migration and apoptosis.

Role of KCNB1 in the prognosis of gliomas and autophagy modulation

Increasing evidence suggests that ion channel genes play an important role in the progression of gliomas. However, the mechanisms by which ion channel genes influence the progression of glioma are not fully understood. We identified KCNB1 as a novel ion gene, associated with malignant progression and favorable overall survival (OS) and progression-free survival (PFS) in glioma patients from three datasets (CGGA, GSE16011 and REMBRANDT). Moreover, we characterized a novel function of autophagy induction accompanied by increased apoptosis and reduced proliferation and invasion of glioma cells for KCNB1. KEGG pathway analysis and in vitro studies suggested that the ERK pathway is involved in KCNB1-mediated regulation of autophagy, which was confirmed by inhibition of KCNB1-induced autophagy by using a selective ERK1/2 inhibitor (U0126) or siERK1/2. In vivo studies showed that KCNB1 induced autophagy while inhibiting tumor growth and increasing survival. Overall, our studies define KCNB1 as a novel prognostic factor for gliomas that exerts its tumor suppressive function through autophagy induction.

IGFBP6 Regulates Cell Apoptosis and Migration in Glioma.

The insulin-like growth factor binding protein 6 (IGFBP6), as an inhibitor of IGF-II actions, plays an important role in inhibiting survival and migration of tumor cells. In our study, we intended to demonstrate the biological function of IGFBP6 in the development of glioma and its clinical significance. Firstly, Western blot and immunohistochemistry revealed that the expression of IGFBP6 inversely correlated with glioma grade. Secondly, multivariate analysis with the Cox proportional hazards model and Kaplan-Meier analysis indicated that IGFBP6 could be an independent prognostic factor for the survival of glioma patients. In addition, overexpression of IGFBP6 induced glioma cell apoptosis, and depletion of IGFBP6 had the opposite action. Finally, overexpression of IGFBP6 inhibited migration of glioma cells, and depletion of IGFBP6 had the opposite action. Together our findings suggest that IGFBP6 might be an important regulator and prognostic factor for glioma.

Up-Regulation of Long Non-Coding RNA AB073614 Predicts a Poor Prognosis in Patients with Glioma.

Dysregulated long noncoding RNAs (lncRNAs) have been found in human diseases, especially in cancer. Emerging evidence indicates that dysregulated lncRNAs are implicated in tumorigenesis and cancer progression. LncRNA AB073614 characterized as a new candidate lncRNA promotes the development of ovarian cancer. However, the role of lncRNA AB073614 in human gliomas remains unknown. The expression of AB073614 was detected in 65 glioma tissues and 13 normal brain tissues by qRT-PCR, showing that lncRNA AB073614 expression was significantly up-regulated in cancerous tissues compared with normal brain tissues (p < 0.001), and it was positively correlated with tumor grade (I–II grades vs. III–IV grades, p = 0.013) in glioma patients. Kaplan-Meier analysis demonstrated that increased AB073614 expression contributed to poor overall survival (HR (hazard ratio) = 1.952, 95%CI: 1.202–3.940, p = 0.0129). Further, univariate Cox regression analysis indicated that lncRNA AB073614 overexpression was an unfavorable prognostic factor in gliomas (HR = 1.997, 95%CI: 1.135–3.514, p = 0.016), regardless of the tumor grade (I–II grades vs. III–IV grades, HR = 1.902, 95%CI: 1.066–3.391, p = 0.029). Finally, after adjustment with age, sex, tumor grade and tumor location, multivariate Cox regression analysis suggested that both highly expressed lncRNA AB073614 (HR = 2.606, 95%CI: 1.408–4.824, p = 0.002) and high tumor grade (III–IV grades, HR = 2.720, 95%CI: 1.401–5.282, p = 0.003) could be considered independent poor prognostic indicators for glioma patients. In conclusion, our study suggested that increased lncRNA AB073614 expression may be identified as a poor prognostic biomarker in gliomas.

Ki-67 is a valuable prognostic factor in gliomas: evidence from a systematic review and meta-analysis.

Ki-67 has been widely used as an indicator of cell proliferation in gliomas. However, the role of Ki-67 as a prognostic marker is still undefined. Thus, we conducted a meta-analysis of the published literatures in order to clarify the impact of Ki-67 on survival in glioma cases. Eligible studies were identified in PubMed, EMBASE, ISI Web of Science, Cochrane Central Register of Controlled Trials, Science Direct and Wiley Online Library with the last search updated on August 31, 2014. The clinical characteristics, overall survival (OS) and progression- free survival (PFS) together with Ki-67 expression at different time points were extracted. A total of 51 studies, covering 4,307 patients, were included in the current meta-analysis. The results showed that overexpression of Ki-67 can predict poor OS (HR=1.66, 95%CI: 1.53-1.80; Z=11.87; p=0.000) and poor PFS (HR=1.67, 95%CI: 1.47-1.91; Z=7.67; p=0.000) in gliomas. Moreover, subgroup analyses also indicated that high level of Ki-67 expression was related to poor OS and PFS in glioma patients regardless of region, pathology type, cut-off value and statistical method. In conclusion, the current meta-analysis revealed that Ki-67 expression might be a predicative factor for poor prognosis of glioma patients, emphasizing its importance as a predictor.

Decreased expression of microRNA-107 predicts poorer prognosis in glioma.

The expression level of microRNA-107 (miR-107) has been proved to be decreased in many human malignant cancers. Especially in glioma, accumulating evidence indicates that miR-107 may play important parts in cell proliferation, apoptosis, and invasion in glioma. However, its clinical significance in glioma has not been investigated. This study aims at investigating the relationship between miR-107 expression level and clinical significance and analyzing its value of miR-107 in valuing the prognosis of glioma patients. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure the expression of miR-107 in 80 glioma and 17 normal brain tissues. The results showed the miR-107 expression level in glioma tissues was significantly lower than those in normal brain tissues (p < 0.001). The decreased expression of miR-107 in glioma was positively associated with high WHO grade (p < 0.001), low Karnofsky performance score (KPS) (p < 0.001), and large tumor size (p < 0.001) and had a significant impact on overall survival (OS) (p < 0.001) and progression-free survival (PFS) (p < 0.001) according to Kaplan-Meier survival with log-rank test. Finally, Cox regression analyses showed that low miR-107 expression (p < 0.001) might be an independent prognostic parameter to predict poor prognosis. In conclusion, it is the first data to prove that expression level of miR-107 may be a novel and valuable prognostic factor in glioma.

Accumulation of 2-hydroxyglutarate in gliomas correlates with survival: a study by 3.0-tesla magnetic resonance spectroscopy.

IntroductionPrevious magnetic resonance spectroscopy (MRS) and mass spectroscopy studies have shown accumulation of 2-hydroxyglutarate (2HG) in mutant isocitrate dehydrogenase (IDH) gliomas. IDH mutation is known to be a powerful positive prognostic marker in malignant gliomas. Hence, 2HG accumulation in gliomas was assumed to be a positive prognostic factor in gliomas, but this has not yet been proven. Here, we analyzed 52 patients harboring World Health Organization (WHO) grade II and III gliomas utilizing 3.0-tesla MRS.ResultsMutant IDH gliomas showed significantly higher accumulation of 2HG (median 5.077 vs. 0.000, p =0.0002, Mann–Whitney test). 2HG was detectable in all mutant IDH gliomas, whereas in 10 out of 27 (37.0%) wild-type IDH gliomas, 2HG was below the detectable range (2HG =0) (p =0.0003, chi-squared test). Screening for IDH mutation by 2HG analysis was highly sensitive (cutoff 2HG =1.489 mM, sensitivity 100.0%, specificity 72.2%). Gliomas with high 2HG accumulation had better overall survival than gliomas with low 2HG accumulation (p =0.0401, Kaplan-Meier analysis).Discussion2HG accumulation detected by 3.0-tesla MRS not only correlates well with IDH status, but also positively correlates with survival in WHO grade II and III gliomas.Electronic supplementary materialThe online version of this article (doi:10.1186/s40478-014-0158-y) contains supplementary material, which is available to authorized users.

Expression of TRAP1 predicts poor survival of malignant glioma patients.

TRAP1/Hsp75 (tumor necrosis factor receptor-associated protein 1), a paralogue of the Hsp90 family, has been recently described as a molecular marker and novel therapeutic target in local and metastatic prostate cancer. It has been proved to be associated with tumor invasion and metastasis in various human malignancies. In our study, the protein expression level of TRAP1 in 236 cases of glioma is investigated by immunohistochemistry assay. Statistical analysis was utilized to evaluate the association of TRAP1 with clinicopathological characteristics and prognosis of patients. It was proved that TRAP1 protein expression was increased in glioma compared with that in normal brain tissue. Moreover, TRAP1 immunohistochemical staining was correlated with World Health Organization (WHO) grade and Karnofsky performance score (KPS). Strong positive TRAP1 staining is more frequently detected in glioma of advanced grade or low KPS. It is also demonstrated that TRAP1 could be an independent negative prognostic factor in glioma, for patients with glioma of strong TRAP1 staining tend to have high risk of death. These results proved that TRAP1 is associated with prognosis of glioma, which may also suggest the potential role of TRAP1 in glioma management.

P04.11 * GENETIC POLYMORPHISMS OF EGF 5'-UTR IN PATIENTS WITH GLIOMA: A POSSIBLE PREDICTIVE MARKER OF OUTCOME

BACKGROUND: Epidermal growth factor (EGF) plays an important role in carcinogenesis. An adenine (A) to guanine (G) single nucleotide polymorphism at position 61 in the 5'-untranslated region (5'-UTR) of the EGF gene has been found to be associated with levels of EGF production and contribute to the risk of glioma. However, published data are contradictory. EGF +61G/A polymorphism may contribute to the risk of glioma in different ethnic group. Patients with glioma and GG genotype have been reported to have a risk of poorer outcome than patients with AA genotype. Purpose of this study is to investigate the potential role of this polymorphism in cancer progression and its role as predictive marker of outcome in glioma caucasian patients. METHODS: The significant SNP rs4444903, EGF 61A/G, was analyzed in glioma patients and was determined by means of Polymerase Chain Reaction and Direct Sequencing method from blood samples. Association of this genetic polymorphism with clinical and pathological data of patients was evaluated. RESULTS: We investigated EGF +61G/A polymorphism in 28 glioma patients. EGF +61G allele has been found in 68% of glioma patients (22% G/G genotype and 46% A/G genotype). In astrocytomas, EGF +61G allele represents a 83% frequency; in glioblastomas and in oligodendrogliomas, EGF +61G allele frequency represents respectively 73% and 54%. In WHO IV gliomas, the EGF +61G allele represents a 72% frequency, (27% G/G and 45% A/G ), in WHO III gliomas a 81% frequency (54% G/G and 27% A/G ) and in WHO II gliomas a 33% frequency (80% A/G ). Median PFS of glioblastoma patients was 9 months. 79% of glioblastoma patients with a relapsing disease showed the G/G and A/G genotype. No difference was detected in the others histotypes. CONCLUSIONS: Our data confirm previous studies which reported G allele as a risk factor for glioma in Caucasian. G/A and G/G genotypes seem to be more rappresentative in high grade gliomas . Despite limited number of patients, our study supports the predictive role of EGF 61 A/G polymorphism in GBM. Additional large studies are warranted to confirm the role of EGF polymorphism as indipendent prognostic factor in glioma.

Collaborative overexpression of matrix metalloproteinase-1 and vascular endothelial growth factor-C predicts adverse prognosis in patients with gliomas

Background and aim: Matrix metalloproteinase-1 (MMP-1), a member of the MMP family of zinc-dependent endopeptidases, has been detected to be strongly expressed in gliomas with high tumor grade and to be correlated with increased tumor invasiveness. Vascular endothelial growth factor-C (VEGF-C), which is able to induce MMP-1 transcription, has been found to be upregulated in glioblastoma compared to low grade gliomas and non-neoplastic brain. The aim of the present study was to investigate the clinical significance of the co-expression of MMP-1 and VEGF-C in glioma patients on determining the prognosis. Methods: One hundred and sixteen glioma patients (26 World Health Organization (WHO) grade I, 30 WHO grade II, 30 WHO grade III, and 30 WHO grade IV) and 15 non-neoplastic brain specimens acquired from 15 patients undergoing surgery for epilepsy as control were collected. Immunohistochemistry was used to evaluate the expression of MMP-1 and VEGF-C in glioma and non-neoplastic brain tissues. The correlations of collaborative MMP-1 and VEGF-C expression with selected clinicopathologic parameters and clinical outcome of glioma patients were also assessed. Results: Both MMP-1 and VEGF-C expression were significantly higher in glioma tissues compared to non-neoplastic brain tissues (both P<0.001). Of 116 glioma patients, 68 (58.62%) overexpressed MMP-1 and VEGF-C simultaneously. In addition, combined MMP-1 and VEGF-C expression was significantly associated with WHO grade (P<0.001) and Karnofsky performance status (KPS) score (P=0.01). Moreover, glioma patients expressing both MMP-1 and VEGF-C exhibited markedly poorer overall survival (P<0.001). According to the multivariate analyses, collaborative overexpression of MMP-1 and VEGF-C was found to be an independent prognostic factor for overall survival (P=0.009). Conclusions: Our data demonstrated for the first time that overexpression of both MMP-1 and VEGF-C may be an independent poor prognostic factor in gliomas, suggesting the interaction between MMP-1 and VEGF-C collaboratively stimulated advanced tumor progression and adverse outcome. Inhibiting both MMP-1 and VEGF-C could be a novel therapeutic approach for gliomas.

The expression of cytoglobin as a prognostic factor in gliomas: a retrospective analysis of 88 patients

BackgroundEvidence suggests that cytoglobin (Cygb) may function as a tumor suppressor gene.MethodsWe immunohistochemically evaluated the expression of Cygb, phosphatidylinositol-3 kinase (PI-3K), phosphorylated (p)-Akt, Interleukin-6 (IL-6), tumor necrosis factor-α (TNFα) and vascular endothelial growth factor (VEGF) in 88 patients with 41 high-grade gliomas and 47 low-grade gliomas. Intratumoral microvessel density (IMD) was also determined and associated with clinicopathological factors.ResultsLow expression of Cygb was significantly associated with the higher histological grading and tumor recurrence. A significant negative correlation emerged between Cygb expression and PI3K, p-Akt, IL-6, TNFα or VEGF expression. Cygb expression was negatively correlated with IMD. There was a positive correlation between PI3K, p-Akt, IL-6, TNFα and VEGF expression with IMD.High histologic grade, tumor recurrence, decreased Cygb expression, increased PI3K expression, increased p-Akt expression and increased VEGF expression correlated with patients’ overall survival in univariate analysis. However, only histological grading and Cygb expression exhibited a relationship with survival of patients as independent prognostic factors of glioma by multivariate analysis.ConclusionsCygb loss may contribute to tumor recurrence and a worse prognosis in gliomas. Cygb may serve as an independent predictive factor for prognosis of glioma patients.

Genetic polymorphisms of EGF 5'-UTR in patients with glioma: A possible predictive marker of outcome.

e13009 Background: Epidermal growth factor (EGF) plays an important role in carcinogenesis. An adenine (A) to guanine (G) single nucleotide polymorphism at position 61 in the 5'-untranslated region (5'-UTR) of the EGF gene has been found to be associated with levels of EGF production and contribute to the risk of glioma. However, published data are contradictory. EGF +61G/A polymorphism may contribute to the risk of glioma in different ethnic group. Patients with glioma and GG genotype have been reported to have a risk of poorer otucome than patients with AA genotype. Purpose of this study is to investigate the potential role of this polymorphism in cancer progression and its role as predictive marker of outcome in glioma caucasian patients. Methods: EGF 61A/G polymorphism (rs4444903) was analyzed in glioma patients and was determined by means of Polymerase Chain Reaction and Direct Sequencing method (GenBank reference sequence-accession no. AC005509) from blood samples. Association of this genetic polymorphism with clinical and pathological data of patients was evaluated. Results: We investigated EGF +61G/A polymorphism in 24 glioma patients . EGF +61G allele has been found in 67% of glioma patients (25% G/G genotype and 42% A/G genotype). In astrocytomas, EGF +61G allele represents a 83% frequency; in glioblastomas and in oligodendrogliomas, EGF +61G allele frequency represents respectively 71% and 50%. In WHO IV gliomas, the EGF +61G allele represents a 63% frequency, (27% G/G and 36% A/G ), in WHO III gliomas a 77% frequency (33% G/G and 44% A/G ) and in WHO II gliomas a 50% frequency (100% A/G ). Median PFS of glioblastoma patients was 9 months. 83% of glioblastoma patients with a relapsing disease showed the G/G and A/G genotype. No difference was detected in the others histotypes. Conclusions: Our data conferm previous studies which reported G allele as a risk factor for glioma in Caucasian. G/A and G/G genotypes seem to be more rappresentative in high grade gliomas . Despite limited number of patients, our study supports the predictive role of EGF 61 A/G polymorphism in GBM. Additional large studies are warranted to confirm the role of EGF polymorphism as indipendent prognostic factor in glioma.

Identification of microRNA-205 as a potential prognostic indicator for human glioma

Altered microRNA-205 (miR-205) expression has been found in glioma tissue samples and cell lines; however, the clinical significance of this is unclear. The aim of this study was to confirm the miR-205 expression pattern in human glioma and to investigate its clinical relevance. Quantitative reverse-transcription polymerase chain reaction assays showed that miR-205 expression was significantly lower in glioma tissues than in non-neoplastic brain tissues (P<0.001). Statistical analysis revealed a significant correlation between low miR-205 expression and both high grade glioma (World Health Organization [WHO] criteria, P=0.008) and a low Karnofsky performance status score (P=0.02). Survival analysis demonstrated that the cumulative 5-year overall survival rate of patients with glioma in the high miR-205 expression group was significantly higher than that in the low miR-205 expression group (P<0.001). Multivariate Cox regression analysis further indicated that miR-205 expression (P=0.01) and WHO grade (P=0.01) were independent prognostic indicators of the overall survival of patients with glioma. Moreover, subgroup analyses revealed that the cumulative 5-year overall survival rate of patients with high grade (III–IV) glioma was significantly worse for the low miR-205 expression group than for the high miR-205 expression group (P<0.001), but no significant difference was found for patients with low grade (I–II) glioma (P=0.09). In conclusion, down-regulation of miR-205 was associated with glioma progression. Our data are the first to suggest that miR-205 holds potential as a prognostic factor for glioma, especially for patients with advanced disease.

Prediagnostic body weight and survival in high grade glioma

Greater adiposity has been linked to an increased risk and/or poorer survival in a variety of cancers. We examined whether prediagnostic body weight 1-5 years prior to diagnosis is associated with survival in patients with high grade glioma. The analysis was based on a series of patients with high-grade glioma (N = 853) enrolled in a US-based multicenter case-control study. Subjects reported height and weight 1-5 years prior to interview and at age 21. BMI was categorized according to WHO criteria as underweight (BMI <18.5 kg/m(2)), normal weight (BMI 18.5-24.9 kg/m(2)), overweight (BMI 25-29.9 kg/m(2)) and obese (BMI ≥30 kg/m(2)). Proportional hazards regression was used to estimate hazard ratios (HR) and 95 % confidence intervals (CIs) for glioma-related death according to body mass index (BMI, kg/m(2)). Overall survival was reduced among patients underweight (median survival: 12.0 months) or obese (median: 13.6 months) when compared to patients of normal weight (median: 17.5 months) prior to glioma diagnosis (p = 0.004). In a multivariate model controlling for other prognostic factors, an excess mortality was observed in patients reporting obese body weights 1-5 years prior to study interview when compared to patients with a normal BMI (HR = 1.32; 95 % CI 1.04-1.68). Consistent patterns of association with excess body weight were observed in men and women, and all findings were similar regardless of treatment for glioma. A lower than optimal body weight was associated with a nonsignificant excess mortality in multivariate analysis. Premorbid obesity was significantly associated with a poor patient outcome independent of treatment and established prognostic factors. Excess body weight may be an adverse prognostic factor in glioma, a relationship observed across a spectrum of cancer types. The current findings linking prediagnostic body weight with mortality in high-grade glioma warrant further research.