胶质母细胞瘤中细胞吞噬相关亚型的相互作用、免疫浸润特征和预后建模。

Interaction, immune infiltration characteristics and prognostic modeling of efferocytosis-related subtypes in glioblastoma.

机构信息

Department of Neurosurgery, Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, China.

Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Zhenjiang, China.

出版信息

BMC Med Genomics. 2023 Oct 18;16(1):248. doi: 10.1186/s12920-023-01688-4.

BACKGROUND

Efferocytosis is a biological process in which phagocytes remove apoptotic cells and vesicles from tissues. This process is initiated by the release of inflammatory mediators from apoptotic cells and plays a crucial role in resolving inflammation. The signals associated with efferocytosis have been found to regulate the inflammatory response and the tumor microenvironment (TME), which promotes the immune escape of tumor cells. However, the role of efferocytosis in glioblastoma multiforme (GBM) is not well understood and requires further investigation.

METHODS

In this study, we conducted a comprehensive analysis of 22 efferocytosis-related genes (ERGs) by searching for studies related to efferocytosis. Using bulk RNA-Seq and single-cell sequencing data, we analyzed the expression and mutational characteristics of these ERGs. By using an unsupervised clustering algorithm, we obtained ERG clusters from 549 GBM patients and evaluated the immune infiltration characteristics of each cluster. We then identified differential genes (DEGs) in the two ERG clusters and classified GBM patients into different gene clusters using univariate cox analysis and unsupervised clustering algorithms. Finally, we utilized the Boruta algorithm to screen for prognostic genes and reduce dimensionality, and the PCA algorithm was applied to create a novel efferocytosis-related scoring system.

RESULTS

Differential expression of ERGs in glioma cell lines and normal cells was analyzed by rt-PCR. Cell function experiments, on the other hand, validated TIMD4 as a tumor risk factor in GBM. We found that different ERG clusters and gene clusters have distinct prognostic and immune infiltration profiles. The ERG signature we developed provides insight into the tumor microenvironment of GBM. Patients with lower ERG scores have a better survival rate and a higher likelihood of benefiting from immunotherapy.

CONCLUSIONS

Our novel efferocytosis-related signature has the potential to be used in clinical practice for risk stratification of GBM patients and for selecting individuals who are likely to respond to immunotherapy. This can help clinicians design appropriate targeted therapies before initiating clinical treatment.

背景

噬作用是一种生物学过程，其中吞噬细胞从组织中清除凋亡细胞和小泡。这个过程是由凋亡细胞释放炎症介质引发的，在炎症的解决中起着至关重要的作用。噬作用相关的信号已被发现调节炎症反应和肿瘤微环境（TME），从而促进肿瘤细胞的免疫逃逸。然而，噬作用在多形性胶质母细胞瘤（GBM）中的作用尚不清楚，需要进一步研究。

方法

在这项研究中，我们通过搜索与噬作用相关的研究，对 22 个噬作用相关基因（ERGs）进行了全面分析。我们使用批量 RNA-Seq 和单细胞测序数据，分析了这些 ERGs 的表达和突变特征。通过使用无监督聚类算法，我们从 549 名 GBM 患者中获得了 ERG 聚类，并评估了每个聚类的免疫浸润特征。然后，我们在两个 ERG 聚类中鉴定了差异基因（DEGs），并使用单变量 cox 分析和无监督聚类算法将 GBM 患者分类为不同的基因聚类。最后，我们利用 Boruta 算法筛选预后基因并降低维度，并用 PCA 算法创建了一种新的噬作用相关评分系统。

结果

通过 rt-PCR 分析了胶质瘤细胞系和正常细胞中 ERGs 的差异表达。另一方面，细胞功能实验验证了 TIMD4 是 GBM 中的肿瘤风险因素。我们发现，不同的 ERG 聚类和基因聚类具有不同的预后和免疫浸润特征。我们开发的 ERG 特征提供了对 GBM 肿瘤微环境的深入了解。具有较低 ERG 评分的患者具有更好的生存率和更有可能受益于免疫治疗。