Immunophenotypic signature of primary glioblastoma multiforme: A case of extended progression free survival

Gandhi, Puneet; Khare, Richa; Garg, Nitin; Sorte, Sandeep K

doi:10.12998/wjcc.v5.i6.247

Cited by 9 publications

(7 citation statements)

References 21 publications

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“… no GFAP(+), OLIG2(+), MKI67(+), MGMT(+), ATRX(−) IDH-1(−), TP53(−) 10 months Anghileri et al [ 73 ] PubMed male 43 headache primary total RT/QT, TMZ, bevacizumab yes GFAP(+), VIMENTIN(+), MGMT(−) EGFR(−) 25 months Elena et al [ 73 ] PubMed male 30 seizures primary total QT/RT, TMZ, bevacizumab yes GFAP(+), VIMENTIN(+), MGMT(−) IDH-1(−), EGFR(−) 6 years Chen et al [ 74 ] PubMed female 5 fever, vomiting primary total n.a. yes MGMT(+), S100A1(+), GFAP(+), MKI67(+), IDH-1 wt(−), TP53(+) 2 months Gandhi et al [ 75 ] PubMed female 45 aphasia primary partial QT/RT yes MKI67(+) TP53(+), EGFR(+), TERT(+), IDH-1 wt (−) 26 months Efferth et al [ 76 ] PubMed …”

Section: Resultsmentioning

confidence: 99%

Glioblastoma multiforme: a multi-omics analysis of driver genes and tumour heterogeneity

et al. 2021

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Glioblastoma (GBM) is the most aggressive and common brain cancer in adults with the lowest life expectancy. The current neuro-oncology practice has incorporated genes involved in key molecular events that drive GBM tumorigenesis as biomarkers to guide diagnosis and design treatment. This study summarizes findings describing the significant heterogeneity of GBM at the transcriptional and genomic levels, emphasizing 18 driver genes with clinical relevance. A pattern was identified fitting the stem cell model for GBM ontogenesis, with an upregulation profile for MGMT and downregulation for ATRX, H3F3A, TP53 and EGFR in the mesenchymal subtype. We also detected overexpression of EGFR, NES, VIM and TP53 in the classical subtype and of MKi67 and OLIG2 genes in the proneural subtype. Furthermore, we found a combination of the four biomarkers EGFR, NES, OLIG2 and VIM with a remarkable differential expression pattern which confers them a strong potential to determine the GBM molecular subtype. A unique distribution of somatic mutations was found for the young and adult population, particularly for genes related to DNA repair and chromatin remodelling, highlighting ATRX, MGMT and IDH1. Our results also revealed that highly lesioned genes undergo differential regulation with particular biological pathways for young patients. This multi-omic analysis will help delineate future strategies related to the use of these molecular markers for clinical decision-making in the medical routine.

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Section: Resultsmentioning

confidence: 99%

Glioblastoma multiforme: a multi-omics analysis of driver genes and tumour heterogeneity

et al. 2021

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“…The work of Shervington and Patel[ 28 ] in glioma subtypes suggests a noteworthy variation of TERT protein expression levels in GB when compared with control. Two case reports presented from our lab also correlate hTERT expression to proliferation, stemness, and survival in glioma sub-types[ 13 , 29 ]. In a first-of-its-kind investigation, the correlation between tissue and blood concentrations of hTERT marker was also established by us in glioma[ 30 ].…”

Section: Discussionmentioning

confidence: 99%

“…We noted a raised expression of the inflammatory marker IL-6 in our enrolled glioma patients. Similarly, limited systemic studies available on GB reveal that aberrant production of this circulating cytokine is directly associated with tumor growth and poor survival, demonstrating IL-6 as an independent prognostic factor for survival[ 13 , 24 , 25 ]. These studies suggest that the cytokine plays an important role in the in situ inflammatory response within the tumor.…”

Section: Discussionmentioning

confidence: 99%

“…The plasma concentrations were noted in ng/mL for KYN and TIMP-1, and ng/L for hTERT. IL-6 test results were computed from the patients’ clinical reports and compared with the baseline values earlier established for this marker in the lab[ 13 ]. The standard reference range of each marker was defined and set as per kit insert.…”

Section: Methodsmentioning

confidence: 99%

“…During gliomagenesis, IL-6 executes a more critical role than other interleukins since it predominately triggers the pro-inflammatory cascade. In the last few years, a couple of blood-based investigations analyzing the expression of IL-6 in different grades of glioma suggested that IL-6 expression may indicate disease prognosis[ 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Novel molecular panel for evaluating systemic inflammation and survival in therapy naïve glioma patients

Gandhi¹,

Shrivastava²,

Garg³

et al. 2021

WJCO

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BACKGROUND Inflammation is crucial to tumor progression. A traumatic event at a specific site in the brain activates the signaling molecules, which triggers inflammation as the initial response within the tumor and its surroundings. The educated immune cells and secreted proteins then initiate the inflammatory cascade leading to persistent chronic inflammation. Therefore, estimation of the circulating inflammatory indicators kynurenine (KYN), interleukin-6 (IL-6), tissue-inhibitor of matrix-metalloproteinase-1 and human telomerase reverse transcriptase (hTERT) along with neutrophil-lymphocyte ratio (NLR) has prognostic value. AIM To assess the utility of chosen inflammatory marker panel in estimating systemic inflammation. METHODS The chosen markers were quantitatively evaluated in 90 naive, molecularly sub-typed plasma samples of glioma. A correlation between the markers and confounders was assessed to establish their prognostication power. Follow-up on the levels of the indicators was done 3-mo post-surgery. To establish the validity of circulating KYN, it was also screened qualitatively by dot-immune-assay and by immunofluorescence-immunohistochemistry in tumor tissues. RESULTS Median values of circulating KYN, IL-6, hTERT, tissue-inhibitor of matrix-metalloproteinase-1 and NLR in isocitrate-dehydrogenase-mutant/wildtype and within the astrocytic sub-groups were estimated, which differed from controls, reaching statistical significance ( P < 0.0001). All markers negatively correlated with mortality ( P < 0.0001). Applying combination-statistics, the panel of KYN, IL-6, hTERT and NLR achieved higher sensitivity and specificity (> 90%) than stand-alone markers, to define survival. The inflammatory panel could discriminate between WHO grades, and isocitrate-dehydrogenase-mutant/wildtype and define differential survival between astrocytic isocitrate-dehydrogenase-mutant/wildtype. Therefore, its assessment for precise disease prognosis is indicated. Association of KYN with NLR, IL-6 and hTERT was significant. Cox-regression described KYN, IL-6, NLR, and hTERT as good prognostic markers, independent of confounders. Multivariate linear-regression analysis confirmed the association of KYN and hTERT with inflammation marker IL-6.There was a concomitant significant decrease in their levels in a 3-mo follow-up. CONCLUSION The first evidence-based study of circulating-KYN in molecularly defined gliomas, wherein the tissue expression was found to be concomitant with plasma levels. A non-invasive model for assessing indicators of chronic systemic inflammation is proposed.

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Evaluating the potential of circulating hTERT levels in glioma: can plasma levels serve as an independent prognostic marker?

2017

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Glioma is an aggressive primary Neuro-epithelial tumor with dismal prognosis, since there is a lack of molecular work-up during routine radiological monitoring of the disease. Currently, a number of potential molecular prognostic and predictive biomarkers are being characterized in line with structured diagnosis defined in World Health Organization guidelines 2016. Human-telomerase reverse-transcriptase (hTERT), a marker of proliferation and maintenance of genomic integrity has thus been investigated for its clinical relevance as an independent prognosticator in glioma. Expression of the protein in tumor tissue and in plasma of 72 diffuse glioma patients (astrocytoma) grade II-IV was determined and compared with relevant controls using immunofluorescence-immunohistochemistry and enzyme-linked immuno-sorbent assay. Appropriate statistical tests were applied to establish a correlation between on-site tumor and circulating levels of the marker and its independence of covariates. Expression of the marker in glioma tissues was significantly different from controls (p < 0.0001) and could discriminate within grades with ≥80% sensitivity. The tissue and plasma levels were positively associated with grades (r = 0.8845, p < 0.0001) and (r = 0.2834, p = 0.0158) respectively, while an inverse correlation with overall survival (r = -0.6558, p < 0.0001) and (r = -0.3941, p = 0.0006) respectively, was recorded. Plasma hTERT was significantly correlated with corresponding intra-tumor expression of hTERT (r = 0.2794, p = 0.0175). Multivariate Cox-regression identified plasma hTERT (p < 0.0005) as a prognostic factor; not associated with age, site or extent of resection (p > 0.05). This is the first experimental evidence for association of higher plasma levels of hTERT with overall survival in both low and high grade glioma.

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Immunophenotypic signature of primary glioblastoma multiforme: A case of extended progression free survival

Cited by 9 publications

References 21 publications

Glioblastoma multiforme: a multi-omics analysis of driver genes and tumour heterogeneity

Glioblastoma multiforme: a multi-omics analysis of driver genes and tumour heterogeneity

Novel molecular panel for evaluating systemic inflammation and survival in therapy naïve glioma patients

Evaluating the potential of circulating hTERT levels in glioma: can plasma levels serve as an independent prognostic marker?

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