scholarly journals Nidogen-1 expression is associated with overall survival and temozolomide sensitivity in low-grade glioma patients

Aging ◽  
2021 ◽  
Author(s):  
Baiwei Zhang ◽  
Cheng Xu ◽  
Junfeng Liu ◽  
Jinsheng Yang ◽  
Qinglei Gao ◽  
...  
2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Shuai Liu ◽  
Yanwei Liu ◽  
Guanzhang Li ◽  
Jin Feng ◽  
Li Chen ◽  
...  

Abstract Background As molecular advances have deepened the knowledge on low-grade glioma (LGG), we investigated the effect of higher radiation dose on the survival of IDH-wildtype (IDHwt) LGG. Methods In the current study, 52 IDHwt LGG patients who received radiotherapy were enrolled from the Chinese Glioma Genome Atlas dataset. Radiation doses > 54 Gy were defined as high-dose, whereas doses ≤ 54 Gy were defined as low-dose. We performed univariate and multivariate survival analyses to examine the prognostic role of high-dose radiotherapy. Results In total, the radiation dose ranged from 48.6 Gy to 61.2 Gy, with a median of 55.8 Gy, and 31 patients were grouped into high-dose radiation. Univariate survival analysis indicated that high-dose radiotherapy (p = 0.015), tumors located in the frontal lobe (p = 0.009), and pathology of astrocytoma (p = 0.037) were significantly prognostic factors for overall survival. In multivariate survival analysis, high-dose radiotherapy (p = 0.028) and tumors located in the frontal lobe (p = 0.016) were independently associated with better overall survival. Conclusions In conclusion, high-dose radiotherapy independently improved the survival of IDHwt LGG. This can guide treatments for glioma with known molecular characteristics.


2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii32-iii32
Author(s):  
H Noor ◽  
R Rapkins ◽  
K McDonald

Abstract BACKGROUND Tumour Protein 53 (TP53) is a tumour suppressor gene that is mutated in at least 50% of human malignancies. The prevalence of TP53 mutation is much higher in astrocytomas with reports of up to 75% TP53 mutant cases. Rare cases of TP53 mutation also exist in oligodendroglial tumours (10–13%). P53 pathway is therefore an important factor in low-grade glioma tumorigenesis. Although the prognostic impact of TP53 mutations has been studied previously, no concrete concordance were reached between the studies. In this study, we investigated the prognostic effects of TP53 mutation in astrocytoma and oligodendroglioma. MATERIAL AND METHODS A cohort of 65 matched primary and recurrent fresh frozen tumours were sequenced to identify hotspot exons of TP53 mutation. Exons 1 to 10 were sequenced and pathogenic mutations were mostly predominant between Exons 4 and 8. The cohort was further expanded with 78 low grade glioma fresh frozen tissues and hotspot exons were sequenced. Selecting only the primary tumour from 65 matched tumours, a total of 50 Astrocytoma cases and 51 oligodendroglioma cases were analysed for prognostic effects of TP53. Only pathogenic TP53 mutations confirmed through COSMIC and NCBI databases were included in the over survival and progression-free survival analysis. RESULTS 62% (31/50) of astrocytomas and 16% (8/51) of oligodendrogliomas harboured pathogenic TP53 mutations. Pathogenic hotspot mutations in codon 273 (c.817 C>T and c.818 G>A) was prevalent in astrocytoma with 58% (18/31) of tumours with these mutations. TP53 mutation status was maintained between primary and recurrent tumours in 93% of cases. In astrocytoma, overall survival of TP53 mutant patients was longer compared to TP53 wild-type patients (p<0.01) but was not significant after adjusting for age, gender, grade and IDH1 mutation status. In contrast, astrocytoma patients with specific TP53 mutation in codon 273 showed significantly better survival compared to other TP53 mutant and TP53 wild-type patients combined (p<0.01) in our multivariate analysis. Time to first recurrence (progression-free survival) of TP53 mutant patients was significantly longer than TP53 wild-type patients (p<0.01) after adjustments were made, while TP53 mutation in codon 273 was not prognostic for progression-free survival. In oligodendroglioma patients, TP53 mutations did not significantly affect overall survival and progression-free survival. CONCLUSION In agreement with others, TP53 mutation is more prevalent in Astrocytoma and mutations in codon 273 are significantly associated with longer survival.


2020 ◽  
Vol 11 ◽  
Author(s):  
Yin Qiu Tan ◽  
Yun Tao Li ◽  
Teng Feng Yan ◽  
Yang Xu ◽  
Bao Hui Liu ◽  
...  

BackgroundThe immunotherapy of Glioma has always been a research hotspot. Although tumor associated microglia/macrophages (TAMs) proves to be important in glioma progression and drug resistance, our knowledge about how TAMs influence glioma remains unclear. The relationship between glioma and TAMs still needs further study.MethodsWe collected the data of TAMs in glioma from NCBI Gene Expression Omnibus (GEO) that included 20 glioma samples and 15 control samples from four datasets. Six genes were screened from the Differential Expression Gene through Gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, protein–protein interaction (PPI) network and single-cell sequencing analysis. A risk score was then constructed based on the six genes and patients’ overall survival rates of 669 patients from The Cancer Genome Atlas (TCGA). The efficacy of the risk score in prognosis and prediction was verified in Chinese Glioma Genome Atlas (CGGA).ResultsSix genes, including CD163, FPR3, LPAR5, P2ry12, PLAUR, SIGLEC1, that participate in signal transduction and plasma membrane were selected. Half of them, like CD163, FPR3, SIGLEC1, were mainly expression in M2 macrophages. FPR3 and SIGLEC1 were high expression genes in glioma associated with grades and IDH status. The overall survival rates of the high risk score group was significantly lower than that of the low risk score group, especially in LGG.ConclusionJoint usage of the 6 candidate genes may be an effective method to diagnose and evaluate the prognosis of glioma, especially in Low-grade glioma (LGG).


2020 ◽  
Author(s):  
S.-Y. JING ◽  
L. CHEN ◽  
S. HAN ◽  
N. LIU ◽  
M.-Y. HAN ◽  
...  

Abstract Background: TCF7L2 gene is known as transcription factor 7-like 2 which has been identified as a novel transcription factor epithelial-mesenchymal transition (EMT) in tumor cells at 10q25.3. TCF7L2 may affect cancer progression and plays a central role in cancer proliferation, migration and invasion. However, its clinical and prognostic value have not been researched in glioma. The purpose of our study was to research TCF7L2 expression and evaluate the clinical value of prognosis.Method: We collected glioma specimens including low-grade glioma (n=46)and glioblastoma (n=51) from September 2015 to September 2017.Expression of TCF7L2 in 97 specimens were detected by quantitative real-time PCR (qRT-PCR).The chi-square test was applied to analyze the relationship between TCF7L2 expression and clinicopathological characteristics. The overall survival (OS) was analyzed by binary logistic regression analysis, the survival curves were drew by Kaplan-Meier. Univariate and multivariate analysis were utilized to analyze the relationship between prognosis and clinicopathological characteristics including TCF7L2 expression.RESULTS: Compared with low-grade glioma group, the expression of TCF7L2 was significantly increased (p<0.05). TCF7L2 overexpression was associated with large tumor volume (p=0.03), higher WHO grade (p=0.001), and recurrence (p=0.001). Moreover, Kaplan-Meier analysis proved that overexpressed TCF7L2 was related with poor OS (p< 0.05).The multivariate analysis suggested that TCF7L2 expression was an independent prognostic factor.CONCLUSIONS: Our research proved that TCF7L2 was over- expressed in glioblastoma, and, related with tumor prognosis, which, therefore, could be an independent prognostic factor for glioma patients.


2021 ◽  
Vol 12 ◽  
Author(s):  
Shiyuan Jing ◽  
Lei Chen ◽  
Song Han ◽  
Ning Liu ◽  
MingYang Han ◽  
...  

Background: The TCF7L2 gene is known as transcription factor 7-like 2 which has been identified as a novel transcription factor epithelial-mesenchymal transition (EMT) in tumor cells at 10q25.3. TCF7L2 may affect cancer progression and plays a central role in cancer proliferation, migration, and invasion. However, its clinical and prognostic value have not been researched in glioma. The purpose of our study was to research TCF7L2 expression and evaluate the clinical value of prognosis.Method: We collected glioma specimens including low-grade glioma (n = 46) and glioblastoma (n = 51) from September 2015 to September 2017. Expression of TCF7L2 in 97 specimens was detected by quantitative real-time PCR (qRT-PCR). The chi-square test was applied to analyze the relationship between TCF7L2 expression and clinicopathological characteristics. The overall survival (OS) was estimated by log-rank tests among strata, and the survival curves were drawn by Kaplan-Meier. Univariate and multivariate analysis were utilized to analyze the relationship between prognosis and clinicopathological characteristics including TCF7L2 expression.Results: Compared with the low-grade glioma group, the expression of TCF7L2 was significantly increased in the glioblastoma group (p = 0.001). TCF7L2 overexpression was associated with higher WHO grade (p = 0.001), isocitrate dehydrogenase (IDH) wild-type (p = 0.001), and lack of O(6)-methylguanine-DNA methyltransferase (MGMT) methylation (p = 0.001). Moreover, Kaplan-Meier analysis proved that overexpressed TCF7L2 was associated with poor OS (p = 0.010). The multivariate analysis suggested that TCF7L2 expression was an independent prognostic factor (p = 0.020).Conclusions: Our research proved that TCF7L2 was overexpressed in glioblastoma, and related with tumor long-term prognosis, which, therefore, could be an independent prognostic factor for glioma patients.


2021 ◽  
Author(s):  
Shuai Liu ◽  
Yanwei Liu ◽  
Guanzhang Li ◽  
Jin Feng ◽  
Li Chen ◽  
...  

Abstract PurposeAs molecular advances have deepened the knowledge on low-grade glioma (LGG), we investigated the effect of higher radiation dose on the survival of IDH-wildtype (IDHwt) LGG.MethodsIn the current study, 52 IDHwt LGG patients who received radiotherapy were enrolled from the Chinese Glioma Genome Atlas dataset. Radiation doses > 54 Gy were defined as high-dose, whereas doses ≤ 54 Gy were defined as low-dose. We performed univariate and multivariate survival analyses to examine the prognostic role of high-dose radiotherapy.ResultsIn total, the radiation dose ranged from 48.6 Gy to 61.2 Gy, with a median of 55.8 Gy, and 31 patients were grouped into high-dose radiation. Univariate survival analysis indicated that high-dose radiotherapy (p = 0.015), tumors located in the frontal lobe (p = 0.009), and pathology of astrocytoma (p = 0.037) were significantly prognostic factors for overall survival. In multivariate survival analysis, high-dose radiotherapy (p = 0.028) and tumors located in the frontal lobe (p = 0.016) were independently associated with better overall survival.ConclusionIn conclusion, high-dose radiotherapy independently improved the survival of IDHwt LGG. This can guide treatments for glioma with known molecular characteristics.


Author(s):  
Thomas Santarius ◽  
Lorenzo Bello ◽  
Hugues Duffau

Diffuse low-grade glioma affect young people in their twenties to forties. The management of this disease is tailored to the needs of each individual patient, taking into account their immediate, medium-, and long-term social and professional roles, personal aspirations, and interests, aiming to achieve optimum onco-functional balance. This starts with measurement of velocity of growth, for which a minimum of two scans with an interval of 2–3 months are obtained. The aim of surgery is resection to predefined functional boundary as this achieves most accurate histological diagnosis, best oncological outcome (prolonged time to anaplastic transformation and overall survival) and preserves function. Awake surgery with electrical brain stimulation mapping allows maximizing the degree of resection and minimize the risk of neurological deficit. Value of repeated surgeries as well as radiotherapy, chemotherapy, and molecular markers, such as IDH1 in the management of diffuse low-grade gliomas, is discussed.


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