Published online May 15, 2024. doi: 10.4251/wjgo.v16.i5.2091
Peer-review started: December 10, 2023
First decision: January 5, 2024
Revised: January 17, 2024
Accepted: February 22, 2024
Article in press: February 22, 2024
Published online: May 15, 2024
Processing time: 151 Days and 3.8 Hours
For the first time, we investigated the oncological role of plexin domain-containing 1 (PLXDC1), also known as tumor endothelial marker 7, in hepatocellular carcinoma (HCC).
According to the latest literature reports and the previous research results of our research team, PLXDC1 participates in the regulation of the development mechanism of some common malignant tumors in the digestive system, such as gastric adenocellular carcinoma. However, whether the biological characteristics of PLXDC1 is related to HCC; HCC is one of the most common tumors of the digestive system, so we want to study whether PLXDC1 gene can affect the development of HCC and its possible mechanism.
To explore whether there is a correlation between the expression of PLXDC1 and the occurrence and development of HCC; explore the correlation between the expression of PLXDC1 and the clinical characteristics and clinical prognosis of HCC; analyze whether PLXDC1 can regulate the occurrence and development and related mechanisms of HCC in the tumor microenvironment, and determine whether this gene may be used as a potential biomarker for clinical prognosis evaluation and related immunotherapy.
Using the cancer genome map database, methylation level assessment, tumor immune microenvironment characteristics screening, tumor immune cell surface checkpoint expression, tumor immune dysfunction and exclusion (TIDE) scoring system and other bioinformatics methods to detect the expression of PLXDC1 in HCC, and evaluate the immune evasion potential of PLXDC1 in HCC;The survival time and other relevant clinical features of clinical HCC cases were collected. The mean ± SD of all clinical data were processed using SPSS 23.0 software, GSEA (v 4.2.3) algorithm, Perl (v 5.32.1.1), and the Kaplan-Meier method, and the correlation between PLXD 1 and HCC was analyzed by relevant statistical procedures such as chi-square test and log-rank test; Through immunohistochemical (IHC) staining analysis, real-time quantitative polymerase chain reaction (PCR) by qRT and Western, the expression level of PLXDC1 gene influences the occurrence and development in tissue metabolism, gene metabolism and protein metabolism of HCC.
Overexpression of PLXDC1 in HCC was associated with poor prognosis based on IHC staining, qRT-PCR, and Western blot assays. Univariate and multivariate Cox analyses suggested that PLXDC1 may be an independent prognostic risk factor. Methylation site analysis indicated that the prognosis of HCC patients with high methylation levels was poorer than that of those with low methylation levels. Pathway enrichment analysis of HCC tissues indicated that genes upregulated in the high-PLXDC1 subgroup were enriched in mesenchymal and immune activation signaling, and TIDE assessment revealed that the risk of immune evasion was significantly greater in the high-PLXDC1 subgroup than in the low-PLXDC1 subgroup. A high PLXDC1-related risk score also indicated a poor prognosis, and immune evasion was significantly greater in the high-risk group than in the low-risk group.
As a result of this research analyzing PLXDC1 from multiple biological perspectives, it was displayed that it is a biomarker of poor prognosis for HCC patients, and that it plays a role in determining immune evasion status.
Based on the results of our previous research in gastric cancer, we proposed the idea of whether PLXD1 affects HCC in the digestive system. To this end, we used the macroscopic bioinformatics perspectives and found that the expression of PLXD 1 affected HCC; By sorting out and analyzing the pathological characteristics of clinical cases, we again verified the correlation between the expression of PLXD 1 expression and clinical HCC prognosis from the individualized clinical perspectives; Finally, we used basic experimental methods such as immunohistochemistry staining analysis, real-time quantitative polymerase chain reaction and Western blotting to prove the above conjecture and results from the microscopic metabolic perspectives of tissue metabolism, gene metabolism, tissue metabolism, protein metabolism and so on.