Research Paper Volume 13, Issue 8 pp 11786—11807
Identification of prognostic biomarkers associated with the occurrence of portal vein tumor thrombus in hepatocellular carcinoma
- 1 The Fourth Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen, China
- 2 Department of Science and Education, Shenzhen Hospital of Traditional Chinese Medicine, Shenzhen, China
Received: December 18, 2020 Accepted: March 14, 2021 Published: April 20, 2021https://doi.org/10.18632/aging.202876
How to Cite
Copyright: © 2021 Lin 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.
The occurrence of portal vein tumor thrombus (PVTT) is strongly correlated to the staging and poor prognosis of hepatocellular carcinoma (HCC) patients. However, the mechanisms of PVTT formation remain unclear. This study aimed to investigate differentially expressed genes (DEGs) between primary tumor (PT) and PVTT tissues and comprehensively explored the underlying mechanisms of PVTT formation. The DEGs between PT and paired PVTT tissues were analyzed using transcriptional data from the Gene Expression Omnibus (GEO) database. The expression, clinical relevance, prognostic significance, genetic alternations, DNA methylation, correlations with immune infiltration, co-expression correlations, and functional enrichment analysis of the DEGs were explored using multiple databases. As result, 12 DEGs were commonly down-expressed in PVTT compared with PT tissues among three datasets. The expression of DCN, CCL21, IGJ, CXCL14, FCN3, LAMA2, and NPY1R was progressively decreased from normal liver, PT, to PVTT tissues, whose up-expression associated with favorable survivals of HCC patients. The genetic alternations and DNA methylation of the DEGs frequently occurred, and several methylated CpG sites of the DEGs significantly correlated with outcomes of HCC patients. The immune infiltration in the tumor microenvironment of HCC was correlated with the expression level of the DEGs. Besides, the DEGs and their co-expressive genes participated in the biological processes of extracellular matrix (ECM) organization and focal adhesion. In summary, this study indicated the dysregulation of ECM and focal adhesion might contribute to the formation of PVTT. And the above seven genes might serve as potential biomarkers of PVTT occurrence and prognosis of HCC patients.
PVTT: portal vein tumor thrombus; HCC: hepatocellular carcinoma; DEGs: differentially expressed genes; GEO: Gene Expression Omnibus; ECM: extracellular matrix; TME: tumor microenvironment; TIICs: infiltrating immune cells; PI3K-Akt: phosphoinositide 3-kinase-protein kinase B; MAPK: mitogen-activated protein kinase; OR: odds ratio; TAMs: tumor-associated macrophages; TANs: tumor-associated neutrophils; FC: fold change; OS: overall survival; RFS: relapse free survival; PFS: progression free survival; DCs: dendritic cells; NK cells: natural killer cells.