Systematic Profiling of mRNA Splicing Reveals the Prognostic Predictor and Potential Therapeutic Target for Glioblastoma Multiforme

Zhang, Botao; Wu, Quanyou; Cheng, Shujun; Li, Wenbin

doi:10.1155/2021/4664955

Cited by 5 publications

(5 citation statements)

References 46 publications

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“…CD3D had an impact on the phenotype and in vitro function of immune cells. Previous study has showed that CD3D is closely related to glioblastoma multiforme [ 38 ], cervical cancer [ 39 ], and breast cancer [ 40 ]. Another study showed that CD3D was the target of mir-182-5p and might be used as candidate biomarkers of breast cancer [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

A novel 4 immune-related genes as diagnostic markers and correlated with immune infiltrates in major depressive disorder

et al. 2022

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Background Immune response is prevalently related with major depressive disorder (MDD) pathophysiology. However, the study on the relationship between immune-related genes (IRGs) and immune infiltrates of MDD remains scarce. Methods We extracted expression data of 148 MDD patients from 2 cohorts, and systematically characterized differentially expressed IRGs by using limma package in R software. Then, the LASSO and multivariate logistic regression analysis was used to identify the most powerful IRGs. Next, we analyzed the relationship between IRGs and immune infiltrates of MDD. Finally, GSE76826 was used to to verificate of IRGs as a diagnostic markers in MDD. Results 203 different IRGs s in MDD has been identified (P < 0.05). GSEA revealed that the different IRGs was more likely to be enriched in immune-specific pathways. Then, a 9 IRGs was successfully established to predict MDD based on LASSO. Next, 4 IRGs was obtained by multivariate logistic regression analysis, and AUC for CD1C, SPP1, CD3D, CAMKK2, and IRGs model was 0.733, 0.767, 0.816, 0.800, and 0.861, suggesting that they have a good diagnostic performance. Furthermore, the proportion of T cells CD8, T cells γδ, macrophages M0, and NK cells resting in MDD group was lower than that in the healthy controls, suggesting that the immune system in MDD group is impaired. Simultaneously, CD3D was validated a reliable marker in MDD, and was positively correlated with T cells CD8. GSEA revealed high expression CD3D was more likely to be enriched in immune-specific pathways, and low expression CD3D was more likely to be enriched in glucose metabolism metabolism-specific pathways. Conclusions We applied bioinformatics approaches to suggest that a 4 IRGs could serve as diagnostic markers to provide a novel direction to explore the pathogenesis of MDD.

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Section: Discussionmentioning

confidence: 99%

A novel 4 immune-related genes as diagnostic markers and correlated with immune infiltrates in major depressive disorder

et al. 2022

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“…Coding for a microtubule protein, TUBB3 is overexpressed and related to poor prognoses in various cancers ( Li et al, 2021 ). Zhang et al suggest that exon skip in DCN is associated with patient survival with glioblastoma ( Zhang et al, 2021a ). KIAA1217 shows different splicing in esophageal squamous cell carcinoma ( Ding et al, 2021 ) and intron retention of KIAA1217 has been found in non-small cell lung cancer, but it is not supported by results of RT-PCR ( Langer et al, 2010 ).…”

Section: Discussionmentioning

confidence: 99%

A new molecular subclassification and in silico predictions for diagnosis and prognosis of papillary thyroid cancer by alternative splicing profile

Liang²,

Li³

et al. 2023

Front. Pharmacol.

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Introduction: Papillary thyroid cancer (PTC) is the most common endocrine malignancy. However, different PTC variants reveal high heterogeneity at histological, cytological, molecular and clinicopathological levels, which complicates the precise diagnosis and management of PTC. Alternative splicing (AS) has been reported to be potential cancer biomarkers and therapeutic targets.Method: Here, we aim to find a more sophisticated molecular subclassification and characterization for PTC by integrating AS profiling. Based on six differentially expressed alternative splicing (DEAS) events, a new molecular subclassification was proposed to reclassify PTC into three new groups named as Cluster0, Cluster1 and Cluster2 respectively.Results: An in silico prediction was performed for accurate recognition of new groups with the average accuracy of 91.2%. Moreover, series of analyses were implemented to explore the differences of clinicopathology, molecular and immune characteristics across them. It suggests that there are remarkable differences among them, but Cluster2 was characterized by poor prognosis, higher immune heterogeneity and more sensitive to anti-PD1 therapy. The splicing correlation networks proved the complicated regulation relationships between AS events and splicing factors (SFs). An independent prognostic indicator for PTC overall survival (OS) was established. Finally, three compounds (orantinib, tyrphostin-AG-1295 and AG-370) were discovered to be the potential therapeutic agents.Discussion: Overall, the six DEAS events are not only potential biomarkers for precise diagnosis of PTC, but also the probable prognostic predictors. This research would be expected to highlight the effect of AS events on PTC characterization and also provide new insights into refining precise subclassification and improving medical therapy for PTC patients.

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“…Previous studies have identified alternative splicing as an important oncogenic pathway in high-grade gliomas [ 7 ]. In addition, mRNA splicing profiling has been considered as an approach to identify prognostic predictors and potential therapeutic targets for GBM [ 46 ]. In this work, we have investigated the impact of IDH mutations, the co-deletion of 1p/19q and the G-CIMP phenotype on alternative mRNA splicing and the expression of protein isoforms in diffuse gliomas.…”

Section: Discussionmentioning

confidence: 99%

Impact of IDH Mutations, the 1p/19q Co-Deletion and the G-CIMP Status on Alternative Splicing in Diffuse Gliomas

Zhang

Fritah

Nazarov

et al. 2023

IJMS

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By generating protein diversity, alternative splicing provides an important oncogenic pathway. Isocitrate dehydrogenase (IDH) 1 and 2 mutations and 1p/19q co-deletion have become crucial for the novel molecular classification of diffuse gliomas, which also incorporates DNA methylation profiling. In this study, we have carried out a bioinformatics analysis to examine the impact of the IDH mutation, as well as the 1p/19q co-deletion and the glioma CpG island methylator phenotype (G-CIMP) status on alternative splicing in a cohort of 662 diffuse gliomas from The Cancer Genome Atlas (TCGA). We identify the biological processes and molecular functions affected by alternative splicing in the various glioma subgroups and provide evidence supporting the important contribution of alternative splicing in modulating epigenetic regulation in diffuse gliomas. Targeting the genes and pathways affected by alternative splicing might provide novel therapeutic opportunities against gliomas.

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Systematic Profiling of mRNA Splicing Reveals the Prognostic Predictor and Potential Therapeutic Target for Glioblastoma Multiforme

Cited by 5 publications

References 46 publications

A novel 4 immune-related genes as diagnostic markers and correlated with immune infiltrates in major depressive disorder

A novel 4 immune-related genes as diagnostic markers and correlated with immune infiltrates in major depressive disorder

A new molecular subclassification and in silico predictions for diagnosis and prognosis of papillary thyroid cancer by alternative splicing profile

Impact of IDH Mutations, the 1p/19q Co-Deletion and the G-CIMP Status on Alternative Splicing in Diffuse Gliomas

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