Oncology department, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, P.R. China.
Cancer Med. 2021 Mar;10(5):1848-1859. doi: 10.1002/cam4.3748. Epub 2021 Feb 16.
Since autophagy remains an important topic of investigation, the RNA-sequence profiles of autophagy-related genes (ARGs) can provide insights into predicting low-grade gliomas (LGG) prognosis.
The RNA-seq profiles of autophagic genes and prognosis data of LGG were integrated from the Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA). Univariate Cox analysis and the least absolute shrinkage and selection operator (LASSO) regression model were carried out to identify the differentially expressed prognostic autophagy-related genes. Then, the autophagic-gene signature was formed and verified in TCGA test set and external CGGA cohorts. Time-dependent receiver operating characteristic (ROC) was examined to test the accuracy of this signature feature. A nomogram was conducted to meet the needs of clinicians. Sankey diagrams were performed to visualize the relationship between the multigene signatures and clinic-pathological features.
Twenty-four ARGs were finally identified most relevant to LGG prognosis. According to the specific prediction index formula, the patients were classified into low-risk or high-risk groups. Prognostic accuracy was proved by time-dependent ROC analysis, with AUC 0.9, 0.93, and 0.876 at the survival time of 2-, 3-, and 5-year, respectively, which was superior to the AUC of the isocitrate dehydrogenase (IDH) mutation. The result was confirmed while validated in the TCGA test set and external validation CGGA cohort. A nomogram was constructed to meet individual needs. With a visualization approach, Sankey diagrams show the relationship of the histological type, IDH status, and predict index. In TCGA and CGGA cohorts, both low-risk groups displayed better survival rate in LGG while histological type and IDH status did not show consistency results.
24-ARGs may play crucial roles in the progression of LGG, and LGG patients were effectively divided into low-risk and high-risk groups according to prognostic prediction. Overall, our study will provide novel strategies for clinical applications.
自噬仍然是一个重要的研究课题,因此自噬相关基因 (ARGs) 的 RNA 测序图谱可以为预测低级别胶质瘤 (LGG) 的预后提供见解。
从癌症基因组图谱 (TCGA) 和中国胶质瘤基因组图谱 (CGGA) 中整合了自噬基因的 RNA-seq 图谱和 LGG 的预后数据。进行单因素 Cox 分析和最小绝对值收缩和选择算子 (LASSO) 回归模型,以鉴定差异表达的与预后相关的自噬相关基因。然后,在 TCGA 测试集和外部 CGGA 队列中验证自噬基因特征。通过时间依赖性接收器工作特征 (ROC) 分析来检验该特征的准确性。制作列线图以满足临床医生的需求。绘制 Sankey 图以可视化多基因特征与临床病理特征之间的关系。
最终确定了与 LGG 预后最相关的 24 个 ARG。根据特定的预测指标公式,将患者分为低风险或高风险组。通过时间依赖性 ROC 分析证明了预后准确性,在生存时间为 2、3 和 5 年时,AUC 分别为 0.9、0.93 和 0.876,优于异柠檬酸脱氢酶 (IDH) 突变的 AUC。在 TCGA 测试集和外部验证 CGGA 队列中验证了该结果。构建了一个列线图以满足个人需求。通过可视化方法, Sankey 图显示了组织学类型、IDH 状态和预测指标之间的关系。在 TCGA 和 CGGA 队列中,低风险组在 LGG 中均显示出更好的生存率,而组织学类型和 IDH 状态并未显示出一致性结果。
24-ARGs 可能在 LGG 的进展中发挥关键作用,并且可以根据预后预测将 LGG 患者有效分为低风险和高风险组。总体而言,我们的研究将为临床应用提供新的策略。