Department of Radiology, The First Affiliated Hospital of Jinan University, 510630, Guangzhou, China.
MOE Key Laboratory of Tumor Molecular Biology and Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, College of Life Science and Technology, Institute of Life and Health Engineering, Jinan University, 510632, Guangzhou, China.
Mol Biomed. 2024 Aug 24;5(1):34. doi: 10.1186/s43556-024-00197-9.
Venous thromboembolism (VTE) is a prevalent complication among patients with cancer, contributing significantly to morbidity and mortality. However, the relationship between VTE-related genes (VRGs) and their potential impact on prognosis, immune response, and therapeutic targets in various cancer types remains unclear. Based on the coagulation and complement pathways, we identified hub VRGs that play a role in regulating the immune response in cancer. Specifically, coagulation factor III (F3), plasminogen activator (PLAT) and complement C1s (C1S) were identified as genes that exhibit high expression levels, positively correlating with tumor stemness and copy number variations, while inversely correlating with methylation levels, in particular cancer types. Pan-cancer survival analysis revealed detrimental effects of these VRGs in several cancer types, notably in glioblastoma and lower grade glioma (GMBLGG). Further analysis using receiver operating characteristic (ROC) curves demonstrated a high accuracy of F3, PLAT and C1S in predicting outcomes in GBMLGG, with area under the curve (AUC) values ranging from 0.78 to 0.9. Validation of the prognostic value of these three genes in GMBLGG was conducted using an independent Gene Expression Omnibus (GEO) dataset. Additionally, gene-drug association analysis identified ciclosporin, ouabain and 6- mercaptopurine, which all exhibit immunosuppressive properties, as potential therapeutic options for tumor patients exhibiting high F3, PLAT or C1S expression, respectively. In summary, our findings provide a bioinformatics perspective on VRGs in pan-cancer, highlighting the pivotal roles of F3, PLAT and C1S, which could potentially be therapeutically exploited and targeted in several cancers, especially in GBMLGG.
静脉血栓栓塞症（VTE）是癌症患者常见的并发症，对发病率和死亡率有重大影响。然而，VTE 相关基因（VRGs）与它们在各种癌症类型中的预后、免疫反应和治疗靶点的潜在影响之间的关系尚不清楚。基于凝血和补体途径，我们确定了在癌症中起作用的核心 VRGs，以调节免疫反应。具体而言，凝血因子 III（F3）、纤溶酶原激活物（PLAT）和补体 C1s（C1S）被鉴定为表现出高表达水平的基因，与肿瘤干性和拷贝数变异呈正相关，而与甲基化水平呈负相关，尤其是在某些癌症类型中。泛癌生存分析显示这些 VRGs 在几种癌症类型中具有不利影响，特别是在胶质母细胞瘤和低级别胶质瘤（GMBLGG）中。使用接收器操作特征（ROC）曲线进行的进一步分析表明，F3、PLAT 和 C1S 在预测 GMBLGG 中的结局方面具有很高的准确性，曲线下面积（AUC）值范围为 0.78 至 0.9。使用独立的基因表达综合数据库（GEO）数据集验证了这三个基因在 GMBLGG 中的预后价值。此外，基因-药物关联分析确定了环孢素、哇巴因和 6-巯基嘌呤，它们都具有免疫抑制特性，分别是 F3、PLAT 或 C1S 高表达的肿瘤患者的潜在治疗选择。总之，我们的研究结果从泛癌的角度提供了 VRGs 的生物信息学视角，突出了 F3、PLAT 和 C1S 的关键作用，它们可能在几种癌症中具有治疗潜力和靶向性，特别是在 GMBLGG 中。
