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Research Paper|Volume 12, Issue 24|pp 25172—25188

Vascular endothelial growth factor receptor-2 and its association with tumor immune regulatory gene expression in hepatocellular carcinoma

Ze-Long Liu1,5, Ling-Ling Zhu2,5, Jing-Hua Liu3, Zhang-Ya Pu5, Zhi-Ping Ruan5, Jiang Chen4,5
  • 1Division of Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, China
  • 2Lung Cancer Center, West China Hospital of Sichuan University, Chengdu, Sichuan Province, China
  • 3Department of Hepatobiliary Surgery and Professor Cai’s Laboratory, Linyi People's Hospital, Linyi, Shandong Province, China
  • 4Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang Province, China
  • 5Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA
* Equal contribution
Received: July 29, 2020Accepted: September 9, 2020Published: November 20, 2020
https://doi.org/10.18632/aging.104119

Copyright: © 2020 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Anti-vascular endothelial growth factor (anti-VEGF) drugs have long been the only first-line treatment for advanced or unresectable hepatocellular carcinoma (HCC). Recently, the combination of bevacizumab (an anti-VEGF drug) and atezolizumab (an immune checkpoint blockade, ICB) has been proven to have superior efficacy over sorafenib. However, the complex association between VEGF signaling pathway and tumor immune microenvironment is still largely unknown. Here, we analyzed the RNA sequencing and clinical data of 365 HCC patients obtained from The Cancer Genome Atlas to investigate the potential correlation between VEGF signaling pathway and tumor immune microenvironment, including immune cell infiltration, 66 immune markers, genomic instability, and immune-related pathways. Our study revealed that VEGF signaling pathway score was positively correlated with immune cell infiltration and the expression profile of 66 immune markers. Enrichment analysis indicated that genes differentially expressed between two VEGF score subtypes were enriched in many immune-related Gene Ontology terms. Most importantly, both VEGF signaling pathway and activated CD8+ T cells were positively correlated with prognosis. Our findings suggest the co-activation of VEGF signaling pathway and tumor immune microenvironment in HCC patients, indicating the underlining mechanism of combination therapy including anti-VEGF drugs and ICBs.