Plexin domain-containing 1 may be a biomarker of poor prognosis in hepatocellular carcinoma patients, may mediate immune evasion.

Background: For the first time, we investigated the oncological role of plexin domain-containing 1 (), also known as tumor endothelial marker 7 (TEM7), in hepatocellular carcinoma (HCC).

Aim: To investigate the oncological profile of in HCC.

Methods: Based on The Cancer Genome Atlas database, we analyzed the expression of in HCC. Using immunohistochemistry, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blotting, we validated our results. The prognostic value of in HCC was analyzed by assessing its correlation with clinicopathological features, such as patient survival, methylation level, tumor immune microenvironment features, and immune cell surface checkpoint expression. Finally, to assess the immune evasion potential of in HCC, we used the tumor immune dysfunction and exclusion (TIDE) website and immunohistochemical staining assays.

Results: Based on immunohistochemistry, qRT-PCR, and Western blot assays, overexpression of in HCC was associated with poor prognosis. Univariate and multivariate Cox analyses indicated that might be an independent prognostic factor. In HCC patients with high methylation levels, the prognosis was worse than in patients with low methylation levels. Pathway enrichment analysis of HCC tissues indicated that genes upregulated in the high- subgroup were enriched in mesenchymal and immune activation signaling, and TIDE assessment showed that the risk of immune evasion was significantly higher in the high- subgroup compared to the low- subgroup. The high-risk group had a significantly lower immune evasion rate as well as a poor prognosis, and -related risk scores were also associated with a poor prognosis.

Conclusion: As a result of this study analyzing from multiple biological perspectives, it was revealed that it is a biomarker of poor prognosis for HCC patients, and that it plays a role in determining immune evasion status.