Progress in the application of molecular biomarkers in gliomas

Wang, Jing; Hong, Soon-Kwang; Zhao, Hua; Chen, Zhong Ping; To, Suet

doi:10.1016/j.bbrc.2015.07.148

Cited by 50 publications

(39 citation statements)

References 49 publications

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“…Less is known about the neural tumors, which are characterized by the expression of neurofilament light polypeptide, synaptotagmin I, and overexpression of EGFR [16]. In terms of prognosis, no difference was found between the classical, mesenchymal, and neural subtypes.…”

Section: Glioblastoma Multiforme: a New Lookmentioning

confidence: 99%

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Diagnostic and Therapeutic Biomarkers in Glioblastoma: Current Status and Future Perspectives

Szopa

Burley

Kramer‐Marek

et al. 2017

BioMed Research International

239

220

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Glioblastoma (GBM) is a primary neuroepithelial tumor of the central nervous system, characterized by an extremely aggressive clinical phenotype. Patients with GBM have a poor prognosis and only 3–5% of them survive for more than 5 years. The current GBM treatment standards include maximal resection followed by radiotherapy with concomitant and adjuvant therapies. Despite these aggressive therapeutic regimens, the majority of patients suffer recurrence due to molecular heterogeneity of GBM. Consequently, a number of potential diagnostic, prognostic, and predictive biomarkers have been investigated. Some of them, such as IDH mutations, 1p19q deletion, MGMT promoter methylation, and EGFRvIII amplification are frequently tested in routine clinical practice. With the development of sequencing technology, detailed characterization of GBM molecular signatures has facilitated a more personalized therapeutic approach and contributed to the development of a new generation of anti-GBM therapies such as molecular inhibitors targeting growth factor receptors, vaccines, antibody-based drug conjugates, and more recently inhibitors blocking the immune checkpoints. In this article, we review the exciting progress towards elucidating the potential of current and novel GBM biomarkers and discuss their implications for clinical practice.

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Section: Glioblastoma Multiforme: a New Lookmentioning

confidence: 99%

“…EGFR amplification can be found, nearly exclusively, in patients with a classical subtype of GBM and is very rare in secondary GBMs [16]. However, the role of EGFR amplification as a prognostic biomarker has yielded conflicting results.…”

Section: Rtk Signaling In Gbmmentioning

confidence: 99%

Diagnostic and Therapeutic Biomarkers in Glioblastoma: Current Status and Future Perspectives

Szopa

Burley

Kramer‐Marek

et al. 2017

BioMed Research International

239

220

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“…Numerous efforts have been made to identify prognostic biomarkers for GBM patients, resulting in the determination of O-6-methylguanine-DNA methyltransferase ( MGMT ) gene promoter methylation (2, 3), mutant isocitrate dehydrogenase 1 and 2 (m IDH1/2 ) (4), as well as chromosome 1p/19q co-deletion, as important indicators of tumor malignancy and/or response to specific therapies (5, 6). Novel immunotherapies, which have caused the reconsideration of patient management among multiple malignancies including melanoma (7, 8) and lung cancer (9, 10), have been largely unsuccessful in treating GBM.…”

Section: Introductionmentioning

confidence: 99%

Infiltrating T Cells Increase IDO1 Expression in Glioblastoma and Contribute to Decreased Patient Survival

Zhai

Ladomersky

Lauing

et al. 2017

Clinical Cancer Research

136

137

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Purpose Indoleamine 2,3 dioxygenase 1 (IDO1) mediates potent immunosuppression in multiple preclinical models of cancer. However, the basis for elevated IDO1 expression in human cancer, including the most common primary malignant brain tumor in adults, glioblastoma (GBM), is poorly understood. The major objective of this study is to address this gap in our understanding of how IDO1 expression contributes to the biology of GBM, and whether its level of expression is a determinant of GBM patient outcome. Experimental Design Patient-resected GBM, the cancer genome atlas, human T cell:GBM co-cultures, as well as nu/nu, NOD-scid and humanized (NSG-SGM3-BLT) mice engrafted human GBM, form the basis of our investigation. Results In situ hybridization for IDO1 revealed transcript expression throughout patient-resected GBM, whereas immunohistochemical IDO1 positivity was highly variable. Multivariate statistical analysis revealed that higher levels of IDO1 transcript predict a poor patient prognosis (P=0.0076). GBM IDO1 mRNA levels positively correlated with increased gene expression for markers of cytolytic and regulatory T cells, in addition to decreased patient survival. Humanized mice intracranially-engrafted human GBM revealed an IFNγ-associated T cell-mediated increase of intratumoral IDO1. Conclusions Our data demonstrate that high intratumoral IDO1 mRNA levels correlate with a poor GBM patient prognosis. It also confirms the positive correlation between increased GBM IDO1 levels and human-infiltrating T cells. Collectively, this study suggests that future efforts aimed at increasing T cell-mediated effects against GBM, should consider combinatorial approaches that co-inhibit potential T cell-mediated IDO1 enhancement during therapy.

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“…Indeed, the TMZtreated GBM patients harboring the T allele of the MGMT promoter SNP rs16906252 have shown a better survival, independently of the tumor methylation status [25]. However, with the exception of the establish role of MGMT methylation [26], there are currently no validated genetic biomarkers to predict or to monitor favorable clinical response or resistance to concomitant radio-and TMZ therapies [27]. Therefore, In this perspective, a recent study has associated the suppressor of Lin-12-like (Caenorhabditis elegans) (SEL1L) rs12435998 C allele with a prolonged OS (18 vs. 13 months, P = 0.011) and a better response to TMZbased radio-chemotherapy (i.e., Stupp's protocol) in 55 GBM patients [28].…”

Section: Discussionmentioning

confidence: 99%

Melanocortin Receptor-4 Gene Polymorphisms in Glioblastoma Patients Treated with Concomitant Radio-Chemotherapy

et al. 2017

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Melanocortins are peptides with well-recognized antiinflammatory and neuroprotective activity. No data are currently available on melanocortin receptor-4 (MC4R) gene polymorphisms and tumors, including glioblastomas (GBMs), or their relationship with radiotherapy or chemotherapy. The aim of this study was to evaluate the possible predictive/prognostic role of the MC4R SNPs on GBM patients. Fifty-five patients with a proven diagnosis of GBM, treated with radiotherapy and temozolomide, were consecutively enrolled. MC4R gene SNPs (rs17782313, rs489693, rs8087522, rs17700633) were analyzed by a validated TaqMan® SNP genotyping assays. Univariate and multivariate analyses were performed. A P < 0.0125 (Bonferroni's correction) was considered significant ( Clinicaltrial.gov identifier NCT02458508). The median progression-free survival (PFS) and median overall survival (OS) of these patients were 9.54 (95% CI 5.4-14.3) months and 24.9 (95% CI 17.8-34.6) months, respectively. The MC4R rs489693 AA genotype was significantly associated with a shorter PFS and OS. Indeed, with regard to PFS, patients harboring the rs489693 AA genotype had a median PFS of 2.99 months whereas patients with AC/CC genotypes had a median PFS of 10.82 months (P = 0.009). Interestingly, the rs489693 AA patients also had a lower median OS as compared with the median OS of the AC/CC genotypes (10.75 vs. 29.5 months, respectively, P = 0.0001). This study suggests that the MC4R rs489693 AA genotype is significantly associated with a shorter PFS and OS in patients treated with radiotherapy and temozolomide. These findings represent a relevant effort to identify novel clinical markers for RT-CT therapy in GBM to be validated in future pharmacogenetic clinical trials.

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Progress in the application of molecular biomarkers in gliomas

Cited by 50 publications

References 49 publications

Diagnostic and Therapeutic Biomarkers in Glioblastoma: Current Status and Future Perspectives

Diagnostic and Therapeutic Biomarkers in Glioblastoma: Current Status and Future Perspectives

Infiltrating T Cells Increase IDO1 Expression in Glioblastoma and Contribute to Decreased Patient Survival

Melanocortin Receptor-4 Gene Polymorphisms in Glioblastoma Patients Treated with Concomitant Radio-Chemotherapy

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