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Development of an Immune Infiltration-Related Prognostic Scoring System Based on the Genomic Landscape Analysis of Glioblastoma Multiforme

机译:基于胶质母细胞瘤的基因组景观分析的免疫渗透相关预后评分系统的发展

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Introduction: Glioblastoma multiforme (GBM) is the most common deadly brain malignancy and lacks effective therapies. Immunotherapy acts as a promising novel strategy, but not for all GBM patients. Therefore, classifying these patients into different prognostic groups is urgent for better personalized management. Materials and Methods: The Cell type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm was used to estimate the fraction of 22 types of immune-infiltrating cells, and least absolute shrinkage and selection operator (LASSO) Cox regression analysis was performed to construct an immune infiltration-related prognostic scoring system (IIRPSS). Additionally, a quantitative predicting survival nomogram was also established based on the immune risk score (IRS) derived from the IIRPSS. Moreover, we also preliminarily explored the differences in the immune microenvironment between different prognostic groups. Results: There was a total of 310 appropriate GBM samples (239 from TCGA and 71 from CGGA) included in further analyses after CIBERSORT filtering and data processing. The IIRPSS consisting of 17 types of immune cell fractions was constructed in TCGA cohort, the patients were successfully classified into different prognostic groups based on their immune risk score ( p = 1e-10). What's more, the prognostic performance of the IIRPSS was validated in CGGA cohort ( p = 0.005). The nomogram also showed a superior predicting value. (The predicting AUC for 1-, 2-, and 3-year were 0.754, 0.813, and 0.871, respectively). The immune microenvironment analyses reflected a significant immune response and a higher immune checkpoint expression in high-risk immune group. Conclusion: Our study constructed an IIRPSS, which maybe valuable to help clinicians select candidates most likely to benefit from immunological checkpoint inhibitors (ICIs) and laid the foundation for further improving personalized immunotherapy in patients with GBM.
机译:简介:胶质母细胞瘤多形形(GBM)是最常见的致命脑炎恶性肿瘤,缺乏有效的疗法。免疫疗法充当有前途的新型战略,但不是所有GBM患者。因此,将这些患者分为不同的预后群体是更好的个性化管理的迫切需要。材料和方法:通过估计RNA转录物(Cibersort)算法的相对子集来估计22种免疫渗透细胞的级分,并且对其进行最低绝对收缩和选择操作员(套索)COX回归分析构建免疫浸润相关的预后评分系统(IIRPS)。另外,还基于衍生自IITPS的免疫风险评分(IRS)来建立定量预测存活率。此外,我们还初步探讨了不同预后组之间免疫微环境的差异。结果:在CiberSort滤波和数据处理之后,共有310个适当的GBM样本(来自CGGA的TCGA和71),包括在进一步分析中。由17种免疫细胞级分组成的IITPS在TCGA队列中构建,患者基于免疫风险评分(P = 1E-10)成功分为不同预后基团。更重要的是,在CGGA队列中验证了IITPS的预后性能(P = 0.005)。 NOM图还显示出优越的预测值。 (预测1-,2-和3年的AUC分别为0.754,0.813和0.871)。免疫微环境分析反映了高风险免疫基团中的显着免疫应答和更高的免疫检查点表达。结论:我们的研究构建了一种IITPS,可能有助于帮助临床医生选择最有可能从免疫检查点抑制剂(ICIS)中受益的候选者,并为进一步改善GBM患者的个性化免疫疗法而奠定了基础。

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