Development of a nomogram for prognostic prediction of lower‐grade glioma based on alternative splicing signatures

Yaning Wang; Zihao Wang; Binghao Zhao; Wenlin Chen; Yu Wang; Wenbin Ma

doi:10.1002/cam4.3530

Modulation of transcriptional activity in brain lower grade glioma by alternative splicing

10.7287/peerj.preprints.26482 ◽

2018 ◽

Author(s):

Jin Li ◽

Yang Wang ◽

Xianglian Meng ◽

Hong Liang

Keyword(s):

Transcription Factor ◽

Transcriptional Regulation ◽

Alternative Splicing ◽

Structural Features ◽

Vital Role ◽

Lower Grade ◽

Exon Inclusion ◽

Gene Transcriptional Regulation ◽

Lower Grade Glioma

Proteins that modify the activity of transcription factor (TF), often called modulators, play a vital role in gene transcriptional regulation. Alternative splicing is a critical step of gene processing and it can modulate gene function by adding or removing certain protein domains, and therefore influences the activity of a protein. The objective of this study is to investigate the role of alternative splicing in modulating the transcriptional regulation in brain lower grade glioma (LGG), especially transcription factor ELK1, which is closely related to various diseases, including Alzheimer’s disease and down syndrome. Results showed that changes in the exon inclusion ratio of proteins APP and STK16 are associated with changes in the expression correlation between ELK1 and its targets. Meanwhile, the structural features of the two modulators are strongly associated with the pathological impact of exon inclusion. Our analysis suggests, protein in different splicing level could play different functions on transcription factors, hence induces multiple genes dysregulation.

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Modulation of transcriptional activity in brain lower grade glioma by alternative splicing

10.7287/peerj.preprints.26482v1 ◽

2018 ◽

Author(s):

Jin Li ◽

Yang Wang ◽

Xianglian Meng ◽

Hong Liang

Keyword(s):

Transcription Factor ◽

Transcriptional Regulation ◽

Alternative Splicing ◽

Structural Features ◽

Vital Role ◽

Lower Grade ◽

Exon Inclusion ◽

Gene Transcriptional Regulation ◽

Lower Grade Glioma

Proteins that modify the activity of transcription factor (TF), often called modulators, play a vital role in gene transcriptional regulation. Alternative splicing is a critical step of gene processing and it can modulate gene function by adding or removing certain protein domains, and therefore influences the activity of a protein. The objective of this study is to investigate the role of alternative splicing in modulating the transcriptional regulation in brain lower grade glioma (LGG), especially transcription factor ELK1, which is closely related to various diseases, including Alzheimer’s disease and down syndrome. Results showed that changes in the exon inclusion ratio of proteins APP and STK16 are associated with changes in the expression correlation between ELK1 and its targets. Meanwhile, the structural features of the two modulators are strongly associated with the pathological impact of exon inclusion. Our analysis suggests, protein in different splicing level could play different functions on transcription factors, hence induces multiple genes dysregulation.

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Modulation of transcriptional activity in brain lower grade glioma by alternative splicing

PeerJ ◽

10.7717/peerj.4686 ◽

2018 ◽

Vol 6 ◽

pp. e4686 ◽

Cited By ~ 3

Author(s):

Jin Li ◽

Yang Wang ◽

Xianglian Meng ◽

Hong Liang

Keyword(s):

Transcriptional Regulation ◽

Transcription Factors ◽

Alternative Splicing ◽

Structural Features ◽

Vital Role ◽

Lower Grade ◽

Exon Inclusion ◽

Gene Transcriptional Regulation ◽

Lower Grade Glioma ◽

Alternatively Spliced

Proteins that modify the activity of transcription factors (TFs) are often called modulators and play a vital role in gene transcriptional regulation. Alternative splicing is a critical step of gene processing, and differentially spliced isoforms may have different functions. Alternative splicing can modulate gene function by adding or removing certain protein domains and thereby influence the activity of a protein. The objective of this study is to investigate the role of alternative splicing in modulating the transcriptional regulation in brain lower grade glioma (LGG), especially transcription factor ELK1, which is closely related to various disorders, including Alzheimer’s disease and Down syndrome. The results showed that changes in the exon inclusion ratio of proteins APP and STK16 are associated with changes in the expression correlation between ELK1 and its targets. In addition, the structural features of the two modulators are strongly associated with the pathological impact of exon inclusion. The results of our analysis suggest that alternatively spliced proteins have different functions in modifying transcription factors and can thereby induce the dysregulation of multiple genes.

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RUNX1 and REXO2 are associated with the heterogeneity and prognosis of IDH wild type lower grade glioma

Scientific Reports ◽

10.1038/s41598-021-91382-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Haiwei Wang ◽

Xinrui Wang ◽

Liangpu Xu ◽

Ji Zhang ◽

Hua Cao

Keyword(s):

Transcription Factor ◽

Low Frequency ◽

Tumor Grade ◽

The Cancer Genome Atlas ◽

Lower Grade ◽

Wild Type ◽

Lower Grade Glioma ◽

Cancer Genome Atlas ◽

Worse Prognosis ◽

Genome Atlas

AbstractBased on isocitrate dehydrogenase (IDH) alterations, lower grade glioma (LGG) is divided into IDH mutant and wild type subgroups. However, the further classification of IDH wild type LGG was unclear. Here, IDH wild type LGG patients in The Cancer Genome Atlas and Chinese Glioma Genome Atlas were divided into two sub-clusters using non-negative matrix factorization. IDH wild type LGG patients in sub-cluster2 had prolonged overall survival and low frequency of CDKN2A alterations and low immune infiltrations. Differentially expressed genes in sub-cluster1 were positively correlated with RUNX1 transcription factor. Moreover, IDH wild type LGG patients with higher stromal score or immune score were positively correlated with RUNX1 transcription factor. RUNX1 and its target gene REXO2 were up-regulated in sub-cluster1 and associated with the worse prognosis of IDH wild type LGG. RUNX1 and REXO2 were associated with the higher immune infiltrations. Furthermore, RUNX1 and REXO2 were correlated with the worse prognosis of LGG or glioma. IDH wild type LGG in sub-cluster2 was hyper-methylated. REXO2 hyper-methylation was associated with the favorable prognosis of LGG or glioma. At last, we showed that, age, tumor grade and REXO2 expression were independent prognostic factors in IDH wild type LGG.

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QOLP-37. QUALITATIVE RESEARCH IN LOWER GRADE GLIOMA: UNDERSTANDING SIGNS, SYMPTOMS, AND DISEASE IMPACTS DURING EXPECTANT MANAGEMENT

Neuro-Oncology ◽

10.1093/neuonc/noz175.857 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi206-vi206

Author(s):

Audra Boscoe ◽

Ted Wells ◽

Christina Graham ◽

Caitlin Pohl ◽

Brooke Witherspoon ◽

...

Keyword(s):

Treatment Options ◽

Expectant Management ◽

Signs And Symptoms ◽

Molecular Therapy ◽

Patient Specific ◽

Lower Grade ◽

Concept Elicitation ◽

Post Surgery ◽

Lower Grade Glioma ◽

Isocitrate Dehydrogenase Mutation

Abstract BACKGROUND Patients with lower grade glioma (LGG) (i.e., grade II or III) have limited treatment options. After surgical resection of their tumor, patients will undergo either a period of expectant management (watch and wait) or treatment with adjuvant chemotherapy and/or radiotherapy. Approximately 80% of patients with LGG have an isocitrate dehydrogenase mutation, which is a viable target for molecular therapy. This offers a therapeutic intervention that could potentially delay the need for chemotherapy and/or radiotherapy in select patients. Several prognostic and patient-specific factors contribute to the decision to recommend expectant management, including concerns about the side effects of chemotherapy and radiotherapy. The aim of this project was to understand patients’ signs and symptoms during the expectant management period and how LGG impacts their lives. METHODS Concept elicitation interviews were conducted in the US with patients with LGG as well as key opinion leaders (KOLs) with experience treating patients with LGG. Interview data were analyzed using Atlas.ti, and patient data were reviewed against KOL data. RESULTS Seven patients with ≥ 3 months of expectant management experience and three KOLs were interviewed. During their expectant management periods, patients reported 12 signs/symptoms, mostly related to deficits in cognition. Patients reported 16 impacts across four categories, with a substantial proportion of the impacts identified as negatively affecting emotional function. The signs/symptoms and impacts reported by patients were generally also reported by KOLs. During expectant management, patients typically resume their original quality of life post-surgery, but may also experience anxiety. Patients and KOLs indicated a preference for expectant management and delaying chemotherapy or radiotherapy. CONCLUSIONS Patient and KOL interviews characterized the LGG experience and indicated a preference for expectant management, which may be supported by therapies that delay the initiation of chemotherapy and/or radiotherapy.

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Identification and Validation of an Individualized Prognostic Signature of Lower-Grade Glioma Based on Nine Immune Related Long Non-coding RNA

Clinical Neurology and Neurosurgery ◽

10.1016/j.clineuro.2020.106464 ◽

2021 ◽

pp. 106464

Author(s):

Aierpati Maimaiti ◽

Lei Jiang ◽

Xixian Wang ◽

Xin Shi ◽

Yinan Pei ◽

...

Keyword(s):

Lower Grade ◽

Prognostic Signature ◽

Non Coding Rna ◽

Lower Grade Glioma ◽

Long Non Coding Rna

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The Role of Surgery in IDH-Wild-Type Lower-Grade Gliomas: Threshold at a High Extent of Resection Should be Pursued

Neurosurgery ◽

10.1093/neuros/nyab052 ◽

2021 ◽

Author(s):

Peng Wang ◽

Chen Luo ◽

Peng-jie Hong ◽

Wen-ting Rui ◽

Shuai Wu

Keyword(s):

Cox Regression ◽

Progression Free Survival ◽

Extent Of Resection ◽

Lower Grade ◽

Wild Type ◽

Cox Regression Analysis ◽

Kaplan Meier ◽

Lower Grade Glioma ◽

Clinical Benefits

Abstract BACKGROUND While maximizing extent of resection (EOR) is associated with longer survival in lower-grade glioma (LGG) patients, the number of cases remains insufficient in determining a EOR threshold to elucidate the clinical benefits, especially in IDH-wild-type LGG patients. OBJECTIVE To identify the effects of EOR on the survival outcomes of IDH-wild-type LGG patients. METHODS IDH-wild-type LGG patients were retrospectively reviewed. The effect of EOR and other predictor variables on overall survival (OS) and progression-free survival (PFS) was analyzed using Cox regression models and the Kaplan-Meier method. RESULTS A total of 94 patients (median OS: 48.9 mo; median follow-up: 30.6 mo) were included in this study. In the multivariable Cox regression analysis, postoperative residual volume was associated with prolonged OS (HR = 2.238; 95% confidence interval [CI], 1.130-4.435; P = .021) and PFS (HR = 2.075; 95% CI, 1.113-3.869; P = .022). Thresholds at a minimum EOR of 97.0% or a maximum residue of 3.0 cm3 were necessary to impact OS positively. For the telomerase reverse transcriptase (TERT)p-wild-type group, such an association was absent. Significant differences in survival existed between the TERTp-wild-type and mutant patients who underwent relatively incomplete resections (residual ≥2.0 cm3 + TERTp wild type: median OS of 62.6 mo [95% CI: 39.7-85.5 mo]; residual ≥2.0 cm3 + TERTp mutant: median OS of 20.0 mo [95% CI:14.6-25.4 mo]). CONCLUSION Our results support the core role of maximal safe resection in the treatment of IDH-wild-type LGGs, especially for IDH-wild-type + TERTp-mutant LGGs. Importantly, the survival benefits of surgery could only be elucidated at a high EOR cut-off point.

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