Sex difference of mutation clonality in diffuse glioma evolution

Zhang, Hongyi; Liao, Jianlong; Zhang, Xinxin; Zhao, Erjie; Liang, Xin; Luo, Shangyi; Shi, Jian; Yu, Fulong; Xu, Jiu Hua; Shen, Weitao; Li, Yixue; Xiao, Yun; Li, Xia

doi:10.1093/neuonc/noy154

Cited by 42 publications

(38 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Surgery and the combined treatment with radiotherapy and chemotherapy were also bene cial to the prognosis of GBM. Above-mentioned ndings have good agreements with other studies [4,11,[29][30][31][32][33].…”

Section: Discussionsupporting

confidence: 91%

Prognostic Factors and Diseases-Specific Survival Outcome in Patients with Glioblastoma: A Population-Based Study

Song

Zhang

et al. 2020

Preprint

View full text Add to dashboard Cite

ObjectiveThis study aimed to determine the prognostic factors for disease-specific survival (DSS) of glioblastoma (GBM) and establish a corresponding effective nomogram for clinical prediction.Methods This study was based on Surveillance, Epidemiology, and End Results database between 2004 and 2015. Kaplan-Meier survival analysis was used to evaluate the effect of various prognostic factors on DSS. Lasso regression was used to determine the independent prognostic factors of DSS and multivariate cox regression analysis was performed correspondingly. Additional restricted cubic spline cox regression was used to analyze the trend of the risk effect (hazard ratio) of continuous variables on DSS. Based on the multivariate cox regression model, a nomogram was established to predict DSS. ResultsThe average age at diagnosis of all enrolled patients was 59.8±12.2 years, of which 40.5% were women and 59.5% were men. Lasso regression analysis showed that age at diagnosis, sex, marital status, race, tumor size, primary site, laterality, surgery, radiotherapy and chemotherapy, radiotherapy sequence with surgery, and year of diagnosis were independent prognostic factors for DSS. Multivariate cox regression analysis showed that elderly, males, unmarried status, larger tumors were all risk factors for DSS. Restricted cubic spline cox regression showed that the risk of death from GBM was significantly increased for the elderly, especially older than 75 years. When the tumor was smaller than 75mm, an increasing risk linearly was associated with DSS, but the risk effect remained constant after 75mm. Constructing the nomogram to predict the DSS probability of 1-, 3- and 5-year respectively, and its good predictive performance was proved by the calibration curve.ConclusionThe advanced age was one of the significant risk factors for GBM. How the change of tumor size affected DSS needed further study and discussion. The established nomogram was robust in predicting 1-, 3-, and 5- year DSS.

show abstract

Section: Discussionsupporting

confidence: 91%

Prognostic Factors and Diseases-Specific Survival Outcome in Patients with Glioblastoma: A Population-Based Study

Song

Zhang

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…The patients with darker (lighter) red color indicate the poorer (better) clinical outcome. B, The flow chart of identification of key bifurcated paths [Color figure can be viewed at wileyonlinelibrary.com]key prognostic gene in GBM, IDH1 (mainly R132H for an amino acid change) was subclonal in 6/24(25%) mutated samples, which kept line with the previous studies 19,39.…”

supporting

confidence: 71%

Identifying bifurcated paths with differential function impact in glioblastomas evolution

Zhang

Xie

Quan

et al. 2020

Intl Journal of Cancer

Self Cite

View full text Add to dashboard Cite

The evolutionary dynamics of human cancers has been investigated popularly and several bifurcated paths in cancer evolutionary trajectories are revealed to be with differential outcomes and phenotypes. However, whether such bifurcated paths exist in glioblastoma (GBM) remains unclear. In 385 GBM samples, through determining the clonal status of cancer driver events and inferring their temporal order, we constructed a temporal map of evolutionary trajectories at the patient population level. By investigating the differential impact on clinical outcome, we identified four key bifurcated paths, namely, "chromosome 10 copy number loss (ie, 10 loss) ! chromosome 19 copy number gain (ie, 19 gain): 10 loss ! 13q loss"; "10 loss ! 19 gain: 10 loss ! 15q loss"; "10 loss ! 19 gain: 10 loss ! 6q loss" and "10 loss ! 19 gain: 10 loss ! 16q loss". They formed a core multibranches path, with 10 loss being regarded as the common earliest event followed by 19 gain and four other departure events (13q loss, 15q loss, 6q loss and 16q loss), which may account for their difference in genome instability and patient survival time. Compared to "10 loss ! 19 gain", the patients with "10 loss ! 13q loss" had higher telomerase activity. Notably, there were obvious discrepancies in immune activity and immune cell infiltration level between patients with "10 loss ! 13q/16q loss" and "10 loss ! 19 gain", highlighting the bifurcated paths' effect on tumor immune microenvironment. In summary, our study identifies four key bifurcated paths in GBM for the first time, suggesting the feasibility of patient stratification and prognosis prediction based on key bifurcated paths.

show abstract

“…In contrast, mutations in genes of receptor tyrosine kinase signalling pathways were more often clonal in males with lower grade gliomas. 18 Using data available in the public domain, it was described that female glioblastoma patients had lower volumes of necrosis at diagnosis than male patients and that the level of necrosis correlated with MYC activity in females, but was linked to P53 activity in males, consistent with the notion that there are sex-specific mechanisms of necrosis in glioblastoma. 19 Heat maps of the TCGA glioblastoma cohort showed distinct patterns of female-specific and male-specific transcriptome components.…”

Section: Sex-specific Tumour Biologymentioning

confidence: 79%

Sex-specific aspects of epidemiology, molecular genetics and outcome: primary brain tumours

Rhun

Weller

2020

ESMO Open

View full text Add to dashboard Cite

Recent years have seen a great interest in sex-specific aspects of many diseases, including cancer, in part because of the assumption that females have often not been adequately represented in early drug development and determination of safety, tolerability and efficacy in clinical trials. Brain tumours represent a highly heterogeneous group of neoplastic diseases with strong variation of incidence by age, but partly also by sex. Most gliomas are more common in men whereas meningiomas, the most common primary intracranial tumours, are more common in females. Potential sex-specific genetic risk factors and specific sex biology have been reported in a tumour-specific manner. Several small studies have indicated differences in tolerability and safety of, as well as benefit from, treatment by sex, but no conclusive data have been generated. Exploring sex-specific aspects of neuro-oncology should be studied more systematically and in more depth in order to uncover the biological reasons for known sex differences in this disease.

show abstract

Sex difference of mutation clonality in diffuse glioma evolution

Cited by 42 publications

References 29 publications

Prognostic Factors and Diseases-Specific Survival Outcome in Patients with Glioblastoma: A Population-Based Study

Prognostic Factors and Diseases-Specific Survival Outcome in Patients with Glioblastoma: A Population-Based Study

Identifying bifurcated paths with differential function impact in glioblastomas evolution

Sex-specific aspects of epidemiology, molecular genetics and outcome: primary brain tumours

Contact Info

Product

Resources

About