The Fourth Clinical Medical School, Guangzhou University of Chinese Medicine, Shenzhen, China.
Department of Science and Education, Shenzhen Hospital of Traditional Chinese Medicine, Shenzhen, China.
Aging (Albany NY). 2021 Apr 20;13(8):11786-11807. doi: 10.18632/aging.202876.
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 , , , , , , and 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.
门静脉癌栓(PVTT)的发生与肝细胞癌(HCC)患者的分期和预后不良密切相关。然而,PVTT 形成的机制仍不清楚。本研究旨在探讨原发性肿瘤(PT)和 PVTT 组织之间差异表达基因(DEGs),并全面探讨 PVTT 形成的潜在机制。使用来自基因表达综合数据库(GEO)的转录组数据分析 PT 和配对 PVTT 组织之间的 DEGs。使用多个数据库探索 DEGs 的表达、临床相关性、预后意义、遗传改变、DNA 甲基化、与免疫浸润的相关性、共表达相关性和功能富集分析。结果显示,在三个数据集的比较中,共有 12 个 DEGs 在 PVTT 中较 PT 组织低表达。 、 、 、 、 、 的表达从正常肝脏、PT 到 PVTT 组织逐渐降低,其高表达与 HCC 患者的良好生存相关。DEGs 的遗传改变和 DNA 甲基化频繁发生,几个 DEGs 的甲基化 CpG 位点与 HCC 患者的结局显著相关。HCC 肿瘤微环境中的免疫浸润与 DEGs 的表达水平相关。此外,DEGs 及其共表达基因参与细胞外基质(ECM)组织和焦点粘连的生物学过程。综上所述,本研究表明 ECM 和焦点粘连的失调可能导致 PVTT 的形成。并且上述七个基因可能作为 PVTT 发生和 HCC 患者预后的潜在生物标志物。