Liu Qing, Bao Hongbo, Zhang Sibin, Song Tianjun, Li Chenlong, Sun Guiyin, Sun Xiaoyang, Fu Tianjiao, Wang Yujie, Liang Peng
Department of Neurosurgery, Harbin Medical University Cancer Hospital, Harbin, China.
Department of Medicine II, University Hospital LMU Munich, Munich, Germany.
Front Genet. 2023 Feb 24;14:1096792. doi: 10.3389/fgene.2023.1096792. eCollection 2023.
Gliomas are brain tumors that arise from glial cells, and they are the most common primary intracranial tumors with a poor prognosis. Cellular senescence plays a critical role in cancer, especially in glioma. In this study, we constructed a senescence-related lncRNA (SRlncRNA) signature to assess the prognosis of glioma. The Cancer Genome Atlas was used to collect SRlncRNA transcriptome profiles and clinical data about glioma. Patients were randomized to training, testing, and whole cohorts. LASSO and Cox regression analyses were employed to construct the SRlncRNA signature, and Kaplan-Meier (K-M) analysis was performed to determine each cohort's survival. Receiver operating characteristic (ROC) curves were applied to verify the accuracy of this signature. Gene set enrichment analysis was used to visualize functional enrichment (GSEA). The CIBERSORT algorithm, ESTIMATE and TIMER databases were utilized to evaluate the differences in the infiltration of 22 types of immune cells and their association with the signature. RT-qPCR and IHC were used to identify the consistency of the signature in tumor tissue. An SRlncRNA signature consisting of six long non-coding RNAs (lncRNAs) was constructed, and patients were divided into high-risk and low-risk groups by the median of their riskscore. The KM analysis showed that the high-risk group had worse overall survival, and the ROC curve confirmed that the riskscore had more accurate predictive power. A multivariate Cox analysis and its scatter plot with clinical characteristics confirmed the riskscore as an independent risk factor for overall survival. GSEA showed that the GO and KEGG pathways were mainly enriched in the immune response to tumor cells, p53 signaling pathway, mTOR signaling pathway, and Wnt signaling pathway. Further validation also yielded significant differences in the risk signature in terms of immune cell infiltration, which may be closely related to prognostic differences, and qRT-PCR and IHC confirmed the consistency of the expression differences in the major lncRNAs with those in the prediction model. Our findings indicated that the SRlncRNA signature might be used as a predictive biomarker and that there is a link between it and immune infiltration. This discovery is consistent with the present categorization system and may open new avenues for research and personalized therapy.
神经胶质瘤是起源于神经胶质细胞的脑肿瘤,是最常见的原发性颅内肿瘤,预后较差。细胞衰老在癌症尤其是神经胶质瘤中起着关键作用。在本研究中,我们构建了一个衰老相关lncRNA(SRlncRNA)特征来评估神经胶质瘤的预后。利用癌症基因组图谱收集SRlncRNA转录组谱和神经胶质瘤的临床数据。患者被随机分为训练组、测试组和全队列组。采用LASSO和Cox回归分析构建SRlncRNA特征,并进行Kaplan-Meier(K-M)分析以确定每个队列的生存率。应用受试者工作特征(ROC)曲线验证该特征的准确性。使用基因集富集分析来可视化功能富集(GSEA)。利用CIBERSORT算法、ESTIMATE和TIMER数据库评估22种免疫细胞浸润的差异及其与该特征的关联。采用RT-qPCR和免疫组化(IHC)鉴定肿瘤组织中该特征的一致性。构建了一个由6个长链非编码RNA(lncRNA)组成的SRlncRNA特征,并根据风险评分的中位数将患者分为高风险组和低风险组。K-M分析表明,高风险组的总生存期较差,ROC曲线证实风险评分具有更准确的预测能力。多变量Cox分析及其与临床特征的散点图证实风险评分是总生存期的独立危险因素。GSEA显示,GO和KEGG通路主要富集于对肿瘤细胞的免疫反应、p53信号通路、mTOR信号通路和Wnt信号通路。进一步验证还发现免疫细胞浸润方面的风险特征存在显著差异,这可能与预后差异密切相关,qRT-PCR和IHC证实主要lncRNA的表达差异与预测模型中的差异一致。我们的研究结果表明,SRlncRNA特征可能用作预测生物标志物,并且它与免疫浸润之间存在联系。这一发现与当前的分类系统一致,可能为研究和个性化治疗开辟新途径。