Tumor mutational burden is associated with poor outcomes in diffuse glioma

Wang, Lihong; Ge, Jia; Yang, Lan; Shi, Yu; Luo, Ying; Tan, Yuhuan; Liang, Mei; Deng, Song; Zhang, Xia; Wang, Wenying; Tan, Yaoyao; Xu, Yuanyuan; Luo, Tao

doi:10.1186/s12885-020-6658-1

Cited by 61 publications

(69 citation statements)

References 25 publications

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“…3). Very low TMB is associated with favorable survival in WHO grade III anaplastic astrocytoma, but not in WHO grade IV GBM 9,13 . Indeed, we confirmed no survival differences in immunotherapynaïve primary (n = 277) or rGBM (n = 132) 11 patient cohorts upon stratification by TMB (Fig.…”

Section: Resultsmentioning

confidence: 94%

Very low mutation burden is a feature of inflamed recurrent glioblastomas responsive to cancer immunotherapy

et al. 2021

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Several immunotherapy clinical trials in recurrent glioblastoma have reported long-term survival benefits in 10–20% of patients. Here we perform genomic analysis of tumor tissue from recurrent WHO grade IV glioblastoma patients acquired prior to immunotherapy intervention. We report that very low tumor mutation burden is associated with longer survival after recombinant polio virotherapy or after immune checkpoint blockade in recurrent glioblastoma patients. A relationship between tumor mutation burden and survival is not observed in cohorts of immunotherapy naïve newly diagnosed or recurrent glioblastoma patients. Transcriptomic analyses reveal an inverse relationship between tumor mutation burden and enrichment of inflammatory gene signatures in cohorts of recurrent, but not newly diagnosed glioblastoma tumors, implying that a relationship between tumor mutation burden and tumor-intrinsic inflammation evolves upon recurrence.

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Section: Resultsmentioning

confidence: 94%

Very low mutation burden is a feature of inflamed recurrent glioblastomas responsive to cancer immunotherapy

et al. 2021

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“…Interestingly, the results of the Kaplan–Meier analysis showed that patients in high TMB group had a poorer prognosis, higher tumor grades, and advanced pathological subtypes. A recent bioinformatics study showed that the high tumor proliferative activity in high TMB patients may lead to a shorter OS of glioma, but more experiments are still needed to validate their findings ( 28 ). As high TMB patients usually benefit from immunotherapy ( 17 , 29 ), higher TMB glioma patients may be able to achieve a better prognosis once immunotherapy is widely utilized in the treatment of glioma.…”

Section: Discussionmentioning

confidence: 99%

Development and Validation of a Tumor Mutation Burden–Related Immune Prognostic Model for Lower-Grade Glioma

Jiang

Tan

et al. 2020

Front. Oncol.

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Tumor mutation burden (TMB) is a useful biomarker to predict prognosis and the efficacy of immune checkpoint inhibitors (ICIs). In this study, we aimed to explore the prognostic value of TMB and the potential association between TMB and immune infiltration in lower-grade gliomas (LGGs). Somatic mutation and RNA-sequencing (RNA-seq) data were downloaded from the Cancer Genome Atlas (TCGA) database. TMB was calculated and patients were divided into high- and low-TMB groups. After performing differential analysis between high- and low-risk groups, we identified six hub TMB and immune-related genes that were correlated with overall survival in LGGs. Then, Gene Set Enrichment Analysis was performed to screen significantly enriched GO terms between the two groups. Moreover, an immune-related risk score system was developed by LASSO Cox analysis based on the six hub genes and was validated with the Chinese Glioma Genome Atlas dataset. Using the TIMER database, we further systematically analyzed the relationships between mutants of the six hub genes and immune infiltration levels, as well as the relationships between the immune-related risk score system and the immune microenvironment in LGGs. The results showed that TMB was negatively correlated with OS and high TMB might inhibit immune infiltration in LGGs. Furthermore, the risk score system could effectively stratify patients into low- and high-risk groups in both the training and validation datasets. Multivariate Cox analysis demonstrated that TMB was not an independent prognostic factor, but the risk score was. Higher infiltration of immune cells (B cells, CD4 + T cells, CD8 + T cells, neutrophils, macrophages, and dendritic cells) and higher levels of immune checkpoints (PD-1, CTLA-4, LAG-3, and TIM-3) were found in patients in the high-risk group. Finally, a novel nomogram model was constructed and evaluated to estimate the overall survival of LGG patients. In summary, our study provided new insights into immune infiltration in the tumor microenvironment and immunotherapies for LGGs.

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“…TMB is a promising biomarker, and studies have shown that high TMB is positively correlated with immunotherapy [39]. In addition, TMB is closely related to the overall survival rate and tumor proliferative activity of glioma patients [40]. Therefore, it is an important reference factor in the treatment and prognosis of glioma.…”

Section: Immunohistochemical Resultsmentioning

confidence: 99%

High Expression of PRMT6 Associated With Prognosis and Immune Infiltration in Glioma

Yang

Wang

Long

et al. 2020

Preprint

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Background: Gliomas are characterised by easy invasion of surrounding tissues, high mortality and poor prognosis. Moreover, with the increase of grade, the prognosis of glioma is increasingly poor and not optimistic. Therefore, biological markers for glioma are needed in clinical work, which can be utilized to detect and evaluate the situation and prognosis of glioma patients. Many studies have found that the protein arginine methyltransferase 6 (PRMT6) expression is elevated in various tumors and is associated with patient prognosis. However, the role of PRMT6 in glioma has not been reported or analyzed. Methods: In this study, we used a variety of tumor related databases to analyze the mechanism of PRMT6 in tumors, especially gliomas, from the perspective of bioinformatics, and carried out relevant experimental verification with tumor tissues extracted from patients during surgery. In addition, we analyzed the relationship between PRMT6 expression and immune infiltration and immune-related cells, and discussed the possible mechanisms. We also discussed the role of PRMT6 expression in glioma from the perspectives of mutation, clinical indicators, enrichment analysis, and immunohistochemical results. Results: PRMT6 is significantly differentially expressed in a variety of tumors and is associated with survival and prognosis. Especially in gliomas, the expression of PRMT6 gradually increased with the increase of grade. In addition, PRMT6 can be used as an independent prognostic risk factor in the nomogram and has been verified in a variety of databases. Conclusions: Our results indicate that high expression of PRMT6 is a potential biomarker for predicting glioma prognosis and progression.

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Tumor mutational burden is associated with poor outcomes in diffuse glioma

Cited by 61 publications

References 25 publications

Very low mutation burden is a feature of inflamed recurrent glioblastomas responsive to cancer immunotherapy

Very low mutation burden is a feature of inflamed recurrent glioblastomas responsive to cancer immunotherapy

Development and Validation of a Tumor Mutation Burden–Related Immune Prognostic Model for Lower-Grade Glioma

High Expression of PRMT6 Associated With Prognosis and Immune Infiltration in Glioma

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