Department of Orthopedics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Division of Spine, Department of Orthopedics, Tongji Hospital affiliated to Tongji University School of Medicine, Shanghai, China.
J Cell Mol Med. 2020 Sep;24(18):10803-10815. doi: 10.1111/jcmm.15705. Epub 2020 Aug 5.
Some studies suggested the prognosis value of immune gene in lower grade glioma (LGG). Recurrence in LGG is a tough clinical problem for many LGG patients. Therefore, prognosis biomarker is required. Multivariate prognosis Cox model was constructed and then calculated the risk score. And differential expressed transcription factors (TFs) and differential expressed immune genes (DEIGs) were co-analysed. Besides, significant immune cells/pathways were identified by single sample gene set enrichment analysis (ssGSEA). Moreover, gene set variation analysis (GSVA) and univariate Cox regression were applied to filter prognostic signalling pathways. Additionally, significant DEIG and immune cells/pathways, and significant DEIG and pathways were co-analysed. Further, differential enriched pathways were identified by GSEA. In sum, a scientific hypothesis for recurrence LGG including TF, immune gene and immune cell/pathway was established. In our study, a total of 536 primary LGG samples, 2,498 immune genes and 318 TFs were acquired. Based on edgeR method, 2,164 DEGs, 2,498 DEIGs and 31 differentials expressed TFs were identified. A total of 106 DEIGs were integrated into multivariate prognostic model. Additionally, the AUC of the ROC curve was 0.860, and P value of Kaplan-Meier curve < 0.001. GATA6 (TF) and COL3A1 (DEIG) were selected (R = 0.900, P < 0.001, positive) as significant TF-immune gene links. Type II IFN response (P < 0.001) was the significant immune pathway. Propanoate metabolism (P < 0.001) was the significant KEGG pathway. We proposed that COL3A1 was positively regulated by GATA6, and by effecting type II IFN response and propanoate metabolism, COL3A1 involved in LGG recurrence.
一些研究表明，免疫基因在低级别胶质瘤（LGG）中具有预后价值。LGG 的复发是许多 LGG 患者面临的一个严峻的临床问题。因此，需要寻找预后生物标志物。本研究构建了多变量预后 Cox 模型并计算了风险评分。同时对差异表达的转录因子（TFs）和差异表达的免疫基因（DEIGs）进行了共分析。此外，还通过单样本基因集富集分析（ssGSEA）鉴定了显著的免疫细胞/通路。再者，通过基因集变异分析（GSVA）和单因素 Cox 回归筛选了预后信号通路。此外，还对显著的 DEIG 和免疫细胞/通路以及显著的 DEIG 和通路进行了共分析。最后，通过 GSEA 鉴定了差异富集的通路。总之，本研究建立了一个包括 TF、免疫基因和免疫细胞/通路的复发 LGG 的科学假说。在本研究中，共获取了 536 例原发性 LGG 样本、2498 个免疫基因和 318 个 TF。基于 edgeR 方法，鉴定了 2164 个差异表达基因、2498 个差异表达免疫基因和 31 个差异表达 TF。共有 106 个差异表达免疫基因被整合到多变量预后模型中。此外，ROC 曲线的 AUC 为 0.860，Kaplan-Meier 曲线的 P 值 <0.001。选择 GATA6（TF）和 COL3A1（DEIG）作为显著的 TF-免疫基因关联（R = 0.900，P <0.001，正相关）。II 型干扰素反应（P <0.001）是显著的免疫通路。丙酸盐代谢（P <0.001）是显著的 KEGG 通路。我们提出 COL3A1 被 GATA6 正向调控，通过影响 II 型干扰素反应和丙酸盐代谢，COL3A1 参与了 LGG 的复发。
