Prognostic role of IDH mutations in gliomas: a meta-analysis of 55 observational studies

Liang, Xiaofeng; Wu, Bin; Fu, Zhiquan; Fěng, Fang; Qiao, Enqi; Li, Qinglin; Sun, Chao; Ge, Minghua

doi:10.18632/oncotarget.4008

Cited by 55 publications

(50 citation statements)

References 75 publications

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“…Furthermore their progression-free survival is significantly increased (Xia et al 2015). This report is in line with reports of higher degrees of cell death in IDH -mutant gliomas.…”

Section: Resultsmentioning

confidence: 99%

Glutamate and α-ketoglutarate: key players in glioma metabolism

Maus

Peters

2016

Amino Acids

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Glioblastoma multiforme (GBM), or grade IV astrocytoma, is the most common type of primary brain tumor. It has a devastating prognosis with a 2-year-overall survival rate of only 26 % after standard treatment, which includes surgery, radiation, and adjuvant chemotherapy with temozolomide. Also lower grade gliomas are difficult to treat, because they diffusely spread into the brain, where extensive removal of tissue is critical. Better understanding of the cancer’s biology is a key for the development of more effective therapy approaches. The discovery of isocitrate dehydrogenase (IDH) mutations in leukemia and glioma drew attention to specific metabolic aberrations in IDH-mutant gliomas. In the center of the metabolic alterations is α-ketoglutarate (αKG), an intermediate metabolite in the tricarboxylic acid (TCA) cycle, and the associated amino acid glutamate (Glu). This article highlights the role of these metabolites in glioma energy and lipid production and indicates possible weak spots of IDH-mutant and IDH-wt gliomas.

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“…Furthermore their progression-free survival is significantly increased (Xia et al 2015). This report is in line with reports of higher degrees of cell death in IDH -mutant gliomas.…”

Section: Resultsmentioning

confidence: 99%

Glutamate and α-ketoglutarate: key players in glioma metabolism

Maus

Peters

2016

Amino Acids

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“…IDH mutation has been proposed to be a favorable prognosticator in LGGs and GBMs. 33,34 We analyzed the correlation of adipokines expression in LGG samples with IDH1 mutation status. For GBM samples IDH1 mutation status was not available in the Xena server.…”

Section: Discussionmentioning

confidence: 99%

NAMPT, GRN, and SERPINE1 signature as predictor of disease progression and survival in gliomas

Vachher

Arora

Burman

et al. 2019

J of Cellular Biochemistry

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Adipose tissue is an important source of adipokines involved in anti‐ and pro‐inflammatory effects. Their involvement in certain cancers such as breast and colon cancer is known but in gliomas it remains unexplored till date. The aim of this study was to assess the status of adipokines as prognostic markers of gliomas (low grade gliomas [LGG] and glioblastoma mutiforme [GBM]). Expression status (messenger RNA [mRNA]), overall survival (OS) and disease‐free survival (DFS) was identified using gene expression profiling interactive analysis server. Clinicopathological analysis and correlation between different adipokines was performed using Xena server. Protein expression status was analyzed using tissue sections from the Human Protein Atlas. Out of 11 adipokines studied visfatin (NAMPT), apelin (APLN), granulin (GRN), serpin peptidase inhibitor/plasminogen activator inhibitor type 1 (PAI‐1) member 1 (SERPINE1), and chemokine (C‐C motif) ligand 2 (CCL2) mRNA levels were significantly upregulated in both LGG and GBM. Interleukin 6 (IL6) mRNA was found be significantly upregulated only in GBM. NAMPT, GRN, SERPINE1, and IL6 showed reduced OS as well as worst DFS for patients having higher mRNA expression in LGG. Increased expression of CCL2 showed worst OS in LGG patients while resistin (RETN) and GRN showed the worst OS in GBM patients. Higher expression of RETN, GRN, IL6, SERPINE1, and CCL2 were found to be positively correlated with shorter DFS in GBM. In the clinicopathological analysis, NAMPT, GRN, IL6, SERPINE1, and CCL2 expressions were significantly associated between the neoplasm histological G2 and G3 grades. Furthermore, expression of NAMPT, GRN, tumor necrosis factor, IL6, SERPINE1, and CCL2 were significantly associated with histological type in LGG patients. NAMPT, GRN, SERPINE1, CCL2, and RETN expression were found to be correlated with each other in gliomas. Finally, NAMPT, GRN, and SERPINE1 were also found to be upregulated using immunohistochemistry in a lower grade and high grade gliomas as compared to normal cells. In conclusion, we have identified key adipokines, namely NAMPT, GRN, and SERPINE1 as potential diagnostic and prognostic markers that might be instrumental in the development and progression of gliomas.

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“…The most important genetic and epigenetic aberrations were found in following cellular signaling pathways: i) Kirsten rat sarcoma viral oncogene homolog (KRAS) and phosphoinositide 3-kinase (PI3K) oncogenic pathways (88% of GBM), ii) the p53 pathway (87% of GBM), iii) cell-cycle regulatory pathway (78% of GBM), and iv) the newly-discovered alterations in metabolic pathways including isocitrate dehydrogenases 1 and 2 (IDH1/2) mutations (10% of GBM). The mutations in IDH1/2 serve also as an independent and important GBM prognostic factor (13)(14)(15). Their routine assessment is now highly recommended in the clinical management of patients with glioma (including GBM) according to the recently updated World Health Organization (WHO) 2016 classification of CNS tumors (16)(17)(18).…”

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confidence: 99%

Advances in Experimental Targeted Therapy and Immunotherapy for Patients with Glioblastoma Multiforme

et al. 2017

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Abstract. Glioblastoma multiforme (GBM) represents the most malignant primary brain tumor in adults with generally dismal prognosis, early clinical deterioration and high mortality. GBM is extremely invasive, characterized by intense and aberrant vascularization and high resistance to multimodal treatment. Standard therapy (surgery, radiotherapy and chemotherapy with temozolomide) has very limited effectiveness, with median overall survival of patients no longer than 15 months. Progress in genetics and epigenetics of GBM over the past decade has revealed various aberrations in cellular signaling pathways, the tumor microenvironment, and pathological angiogenesis. A number of targeted anticancer drugs, such as small-molecule kinase inhibitors and monoclonal antibodies, have been evaluated in clinical trials with newly-diagnosed, as well as recurrent GBM. Unfortunately, to date, only a single antiangiogenic agent, bevacizumab, has been approved for the treatment of recurrent GBM in the USA and Canada. The novel possibilities of cancer immunotherapy, especially immune checkpoint inhibitors, are being evaluated in clinical trials of patients with GBM. The most recent clinical experiences with targeted therapy as well as immunotherapy of GBM are given in this review. The relative lack of success of some of these approaches recently revealed in well-designed randomized clinical trials is also discussed.Glioblastoma multiforme (GBM) belongs to the largest group of primary central nervous system (CNS) tumors, so-called gliomas, which are formed from supporting glial cells in the brain parenchyma (1, 2). GBM represents the most common and most malignant tumor in this class, with an incidence of 3-4/100,000/year (3, 4). GBM is an extremely invasive and difficult to treat tumor, characterized by intense and aberrant vascularization and high resistance to radiotherapy (RT) and chemotherapy (CHT). The current standard of care for patients with newly-diagnosed GBM comprises of neurosurgery and subsequent concomitant chemoradiotherapy by fractionated external-beam RT and systemic temozolomide followed by systemic temozolomide in the adjuvant setting (5). There are only very limited possibilities for the treatment of subsequent recurrences, generally with minimal clinical efficacy (6). Despite intensive multimodal treatment strategies, the median survival of patients with GBM is still 12.1-14.6 months and only 3-5% of patients survive longer than 3 years (7).Enormous progress has been made in the genetics and epigenetics of GBM during the past decade. The Cancer 21Τhis article is freely accessible online.Correspondence to: Jiri Polivka, Department of Neurology, Faculty Hospital Plzen, alej Svobody 80, 304 60, Plzen, Czech Republic. E-mail: polivka@fnplzen.cz Key Words: Glioblastoma multiforme, GBM, targeted therapy, immunotherapy, immune checkpoint inhibitors, PD1 inhibition, CTLA4 inhibition, clinical trials, personalized medicine, review. ANTICANCER RESEARCH 37: 21-34 (2017) [8][9][10][11][12]. The most important genetic...

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Prognostic role of IDH mutations in gliomas: a meta-analysis of 55 observational studies

Cited by 55 publications

References 75 publications

Glutamate and α-ketoglutarate: key players in glioma metabolism

Glutamate and α-ketoglutarate: key players in glioma metabolism

NAMPT, GRN, and SERPINE1 signature as predictor of disease progression and survival in gliomas

Advances in Experimental Targeted Therapy and Immunotherapy for Patients with Glioblastoma Multiforme

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