Wang Wenwen, Li Weilong, Pan Lifang, Li Lingjie, Xu Yasi, Wang Yuqing, Zhang Xiaochen, Zhang Shirong
School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Affiliated Hangzhou First People's Hospital, Hangzhou 310053, China.
Translational Medicine Research Center, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, Hangzhou 310006, China.
Biology (Basel). 2023 Mar 22;12(3):488. doi: 10.3390/biology12030488.
Glioma is the most prevalent and aggressive primary nervous system tumor with an unfavorable prognosis. Microtubule plus-end-related genes (MPERGs) play critical biological roles in the cell cycle, cell movement, ciliogenesis, and neuronal development by coordinating microtubule assembly and dynamics. This research seeks to systematically explore the oncological characteristics of these genes in microtubule-enriched glioma, focusing on developing a novel MPERG-based prognostic signature to improve the prognosis and provide more treatment options for glioma patients. First, we thoroughly analyzed and identified 45 differentially expressed MPERGs in glioma. Based on these genes, glioma patients were well distinguished into two subgroups with survival and tumor microenvironment infiltration differences. Next, we further screened the independent prognostic genes (, , , , , , and ) using 36 prognostic-related differentially expressed MPERGs to construct a signature with risk stratification and prognostic prediction ability. An increased risk score was related to the malignant progression of glioma. Therefore, we also designed a nomogram model containing clinical factors to facilitate the clinical use of the risk signature. The prediction accuracy of the signature and nomogram model was verified using The Cancer Genome Atlas and Chinese Glioma Genome Atlas datasets. Finally, we examined the connection between the signature and tumor microenvironment. The signature positively correlated with tumor microenvironment infiltration, especially immunoinhibitors and the tumor mutation load, and negatively correlated with microsatellite instability and cancer stemness. More importantly, immune checkpoint blockade treatment and drug sensitivity analyses confirmed that this prognostic signature was helpful in anticipating the effect of immunotherapy and chemotherapy. In conclusion, this research is the first study to define and validate an MPERG-based signature closely associated with the tumor microenvironment as a reliable and independent prognostic biomarker to guide personalized choices of immunotherapy and chemotherapy for glioma patients.
胶质瘤是最常见且侵袭性最强的原发性神经系统肿瘤，预后不佳。微管正端相关基因（MPERGs）通过协调微管组装和动力学，在细胞周期、细胞运动、纤毛发生和神经元发育中发挥关键生物学作用。本研究旨在系统探索这些基因在富含微管的胶质瘤中的肿瘤学特征，重点是开发一种基于MPERGs的新型预后特征，以改善预后并为胶质瘤患者提供更多治疗选择。首先，我们全面分析并鉴定了胶质瘤中45个差异表达的MPERGs。基于这些基因，胶质瘤患者被很好地分为两个亚组，这两个亚组在生存和肿瘤微环境浸润方面存在差异。接下来，我们使用36个与预后相关的差异表达MPERGs进一步筛选出独立预后基因（、、、、、和），以构建具有风险分层和预后预测能力的特征。风险评分增加与胶质瘤的恶性进展相关。因此，我们还设计了一个包含临床因素的列线图模型，以促进风险特征在临床中的应用。使用癌症基因组图谱和中国胶质瘤基因组图谱数据集验证了该特征和列线图模型的预测准确性。最后，我们研究了该特征与肿瘤微环境之间的联系。该特征与肿瘤微环境浸润呈正相关，尤其是免疫抑制剂和肿瘤突变负荷，与微卫星不稳定性和癌症干性呈负相关。更重要的是，免疫检查点阻断治疗和药物敏感性分析证实，这种预后特征有助于预测免疫治疗和化疗的效果。总之，本研究是首次定义并验证一种与肿瘤微环境密切相关的基于MPERGs的特征，作为一种可靠且独立的预后生物标志物，以指导胶质瘤患者免疫治疗和化疗的个性化选择。
