Pan-cancer analysis identifies venous thromboembolism-related genes F3, PLAT, and C1S as potential prognostic biomarkers for glioblastoma and lower grade glioma

Sep 21, 2026

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Venous thromboembolism (VTE) is a frequent cancer complication that drives morbidity and mortality. The links between VTE-related genes (VRGs) and prognosis, immune activity, and drug-target potential across cancer types remain unclear. Using coagulation and complement pathway analyses, hub VRGs were identified, with F3, PLAT and C1S showing high expression tied to stemness and copy-number gains, and reduced methylation. Pan-cancer survival and ROC results support prognostic impact in glioblastoma and lower grade glioma (GBMLGG).

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Abstract

Introduction

Zhang et al. Molecular Biomedicine (2024) 5:34 [https://doi.org/10.1186/s43556-024-00197-9](https://doi.org/10.1186/s43556-024-00197-9) Molecular Biomedicine RESEARCH Open Access Pan-cancer analysis identifies venous thromboembolism-related genes F3, PLAT, and C1S as potential prognostic biomarkers for glioblastoma and lower grade glioma Jing Zhang1,2*†, Qian Zhao2†, Yun Du3†, Wannan Wang1,2 and Cuiqing Liu4* Abstract 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. Keywords Venous thromboembolism, Coagulation, Complement, Pan-cancer, Tumor immune microenvironment †Jing Zhang, Qian Zhao andYun Du contributed equally to this work *Correspondence: Jing Zhang [zj6410@jnu.edu.cn](zj6410@jnu.edu.cn)[ ](zj6410@jnu.edu.cn)Cuiqing Liu [13302381081@126.com](13302381081@126.com) 1 Department of Radiology, The First Affiliated Hospital of Jinan University, 510630 Guangzhou, China 2 Present Address: 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 3 Present Address: Department of Nursing, The First Affiliated Hospital of Jinan University, 510630 Guangzhou, China 4 Department of Surgery, The First Affiliated Hospital of Jinan University, 510630 Guangzhou, China © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit [http://creativecommons.o

FAQs

Which VTE-related genes were highlighted as potential prognostic biomarkers?

The study identifies coagulation factor III (F3), plasminogen activator (PLAT), and complement C1s (C1S) as genes associated with prognosis in GBMLGG.

How did the genes relate to tumor stemness, copy-number variation, and methylation?

F3, PLAT, and C1S show high expression positively correlated with tumor stemness and copy-number variations, while inversely correlating with methylation levels in particular cancer types.

How was prognostic performance evaluated for these genes in GBMLGG?

Detrimental effects were observed in pan-cancer survival analysis, and ROC curve analysis showed high predictive accuracy with AUC values ranging from 0.78 to 0.9; validation used an independent GEO dataset.

Sep 21, 2026

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