Background/Objectives: Transcriptome profiling can reveal prognostic biomarkers and therapeutic vulnerabilities for directing clinical care. Currently, there are no biomarkers that can accurately predict patient prognosis regarding tumor growth and the tumor immune microenvironment in vestibular schwannomas. This study aimed to investigate the mechanisms of tumor growth using bulk RNA-seq and single-cell data from patients with vestibular schwannomas.Methods: Gene set variation analysis was used to assess groups with high and low tumor growth using four cohorts of bulk RNA-seq data (210 patients with vestibular schwannoma), 33,081 single cells, and 558 tumor growth-related genes.Results: SIG558, a tumor growth signature gene, was enriched in Schwann cells and microglial cells with high stemness, according to stemness analysis and cell–cell communication analysis of 33,081 single cells. We identified 391 genes that were strongly expressed in Schwann cells with high stemness. In addition, we identified 23 genes related to signal transduction that are important for tumor growth through cell–cell interactions in seven cell types at the single-cell level.Conclusions: Our research demonstrates that the 23 signature genes are potential predictors and prognostic biomarkers for direct medical therapy in patients with vestibular schwannoma, and that they should be prospectively verified using large patient cohorts. These results could potentially be used in precision medicine to develop treatment strategies for vestibular schwannomas by targeting these 23 genes.
背景/目的：转录组分析能够揭示指导临床治疗的预后生物标志物和治疗靶点。目前尚无能够准确预测前庭神经鞘瘤患者肿瘤生长及肿瘤免疫微环境预后的生物标志物。本研究旨在利用前庭神经鞘瘤患者的批量RNA测序数据和单细胞数据探究肿瘤生长机制。 方法：通过整合四组批量RNA测序数据（210名前庭神经鞘瘤患者）、33,081个单细胞数据以及558个肿瘤生长相关基因，采用基因集变异分析方法评估肿瘤生长高、低风险组别。 结果：基于33,081个单细胞的干性分析与细胞间通讯分析发现，肿瘤生长特征基因SIG558在高干性施万细胞和小胶质细胞中显著富集。我们鉴定出391个在高干性施万细胞中强表达的基因，并在单细胞层面识别出7种细胞类型中通过细胞间相互作用影响肿瘤生长的23个信号转导相关基因。 结论：本研究表明这23个特征基因可作为前庭神经鞘瘤患者直接医疗干预的潜在预测因子和预后生物标志物，需通过大规模患者队列进行前瞻性验证。这些发现有望应用于精准医疗领域，通过靶向这23个基因为前庭神经鞘瘤制定治疗策略。
Development of a 23-Gene Signature for Tumor Growth Mechanism in Vestibular Schwannoma
肿瘤(癌症)患者之家