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

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

doi:10.1002/cam4.3530

Cited by 5 publications

(3 citation statements)

References 30 publications

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“…Further, we formulated a nomogram to guide clinical practice in an individualized manner, and its predictive performance was validated across different datasets. Although many previous studies have adopted nomogram models in predicting overall survival of LGG patients, most of them (37)(38)(39) suffered from a lack of external validation. Our study, on the other hand, offered solid external validation with ROC analysis and calibration plot and the nomogram demonstrated to be clinically relevant, discriminant and accurate in predicting survival outcomes.…”

Section: Discussionmentioning

confidence: 99%

Integrated Analysis Reveals Prognostic Value and Immune Correlates of CD86 Expression in Lower Grade Glioma

Qiu

Tian

et al. 2021

Front. Oncol.

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BackgroundCD86 has great potential to be a new target of immunotherapy by regulating cancer immune response. However, it remains unclear whether CD86 is a friend or foe in lower-grade glioma (LGG).MethodsThe prognostic value of CD86 expression in pan-cancer was analyzed using Cox regression and Kaplan-Meier analysis with data from the cancer genome atlas (TCGA). Cancer types where CD86 showed prognostic value in overall survival and disease-specific survival were identified for further analyses. The Chinese Glioma Genome Atlas (CGGA) dataset were utilized for external validation. Quantitative real-time PCR (qRT-PCR), Western blot (WB), and Immunohistochemistry (IHC) were conducted for further validation using surgical samples from Jiangsu Province hospital. The correlations between CD86 expression and tumor immunity were analyzed using the Estimation of Stromal and Immune cells in Malignant Tumours using Expression data (ESTIMATE) algorithm, Tumor IMmune Estimation Resource (TIMER) database, and expressions of immune checkpoint molecules. Gene Set Enrichment Analysis (GSEA) was performed using clusterprofiler r package to reveal potential pathways.ResultsPan-cancer survival analysis established CD86 expression as an unfavorable prognostic factor in tumor progression and survival for LGG. CD86 expression between Grade-II and Grade-III LGG was validated using qRT-PCR and WB. Additionally, CD86 expression in LGG with unmethylated O(6)-methylguanine-DNA-methyltransferase (MGMT) promoter was significantly higher than those with methylated MGMT (P<0.05), while in LGG with codeletion of 1p/19q it was significantly downregulated as opposed to those with non-codeletion (P<2.2*10-16). IHC staining validated that CD86 expression was correlated with MGMT status and X1p/19q subtypes, which was independent of tumor grade. Multivariate regression validated that CD86 expression acts as an unfavorable prognostic factor independent of clinicopathological factors in overall survival of LGG patients. Analysis of tumor immunity and GSEA revealed pivotal role of CD86 in immune response for LGG.ConclusionsIntegrated analysis shows that CD86 is an unfavorable prognostic biomarker in LGG patients. Targeting CD86 may become a novel approach for immunotherapy of LGG.

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Section: Discussionmentioning

confidence: 99%

Integrated Analysis Reveals Prognostic Value and Immune Correlates of CD86 Expression in Lower Grade Glioma

Qiu

Tian

et al. 2021

Front. Oncol.

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“…To date, there are considerable risk models for LGG prognostic and immune prediction. Wang et al (2020 ) developed a nomogram to predict LGG patients’ survival outcomes based on alternative splicing, which performed better than clinical markers such as age, grade, and IDH1 mutation status. Qu et al (2020) and Qu et al (2021a ) constructed prognostic models for glioma using N6-methyladenine-related and autophagy-related genes, respectively.…”

Section: Discussionmentioning

confidence: 99%

A Novel CRISPR/Cas9 Screening Potential Index for Prognostic and Immunological Prediction in Low-Grade Glioma

Xiong

et al. 2022

Front. Genet.

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Glioma is a malignancy with the highest mortality in central nervous system disorders. Here, we implemented the computational tools based on CRISPR/Cas9 to predict the clinical outcomes and biological characteristics of low-grade glioma (LGG). The transcriptional expression profiles and clinical phenotypes of LGG patients were retrieved from The Cancer Genome Atlas and Chinese Glioma Genome Atlas. The CERES algorithm was used to screen for LGG-lethal genes. Cox regression and random survival forest were adopted for survival-related gene selection. Nonnegative matrix factorization distinguished patients into different clusters. Single-sample gene set enrichment analysis was employed to create a novel CRISPR/Cas9 screening potential index (CCSPI), and patients were stratified into low- and high-CCSPI groups. Survival analysis, area under the curve values (AUCs), nomogram, and tumor microenvironment exploration were included for the model validation. A total of 20 essential genes in LGG were used to classify patients into two clusters and construct the CCSPI system. High-CCSPI patients were associated with a worse prognosis of both training and validation set (p < 0.0001) and higher immune fractions than low-CCSPI individuals. The CCSPI system had a promising performance with 1-, 3-, and 5-year AUCs of 0.816, 0.779, 0.724, respectively, and the C-index of the nomogram model reached 0.743 (95% CI = 0.725–0.760). Immune-infiltrating cells and immune checkpoints such as PD-1/PD-L1 and POLD3 were positively associated with CCSPI. In conclusion, the CCSPI had prognostic value in LGG, and the model will deepen our cognition of the interaction between the CNS and immune system in different LGG subtypes.

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“…An increasing number of studies investigated AS as an additional tool for glioma classification. The establishment of a tumor database facilitates bioinformatics analysis on splicing events and the outcome of cancer patients [ 175 ]. In support of the above the first methodologically profiled prognostic models were proposed.…”

Section: Gliomamentioning

confidence: 99%

Alternative RNA Splicing—The Trojan Horse of Cancer Cells in Chemotherapy

Mehterov

Kazakova

Sbirkov

et al. 2021

Genes

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Almost all transcribed human genes undergo alternative RNA splicing, which increases the diversity of the coding and non-coding cellular landscape. The resultant gene products might have distinctly different and, in some cases, even opposite functions. Therefore, the abnormal regulation of alternative splicing plays a crucial role in malignant transformation, development, and progression, a fact supported by the distinct splicing profiles identified in both healthy and tumor cells. Drug resistance, resulting in treatment failure, still remains a major challenge for current cancer therapy. Furthermore, tumor cells often take advantage of aberrant RNA splicing to overcome the toxicity of the administered chemotherapeutic agents. Thus, deciphering the alternative RNA splicing variants in tumor cells would provide opportunities for designing novel therapeutics combating cancer more efficiently. In the present review, we provide a comprehensive outline of the recent findings in alternative splicing in the most common neoplasms, including lung, breast, prostate, head and neck, glioma, colon, and blood malignancies. Molecular mechanisms developed by cancer cells to promote oncogenesis as well as to evade anticancer drug treatment and the subsequent chemotherapy failure are also discussed. Taken together, these findings offer novel opportunities for future studies and the development of targeted therapy for cancer-specific splicing variants.

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

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 5 publications

References 30 publications

Integrated Analysis Reveals Prognostic Value and Immune Correlates of CD86 Expression in Lower Grade Glioma

Integrated Analysis Reveals Prognostic Value and Immune Correlates of CD86 Expression in Lower Grade Glioma

A Novel CRISPR/Cas9 Screening Potential Index for Prognostic and Immunological Prediction in Low-Grade Glioma

Alternative RNA Splicing—The Trojan Horse of Cancer Cells in Chemotherapy

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