Hepatocellular carcinoma (HCC) is the most common primary liver malignancy with no curative treatments. Plexin D1 (PLXND1) is a cellular receptor whose functions have been explored in several human cancers; however, the critical roles of PLXND1 in HCC have rarely been probed. Therefore, the present study attempted to elucidate the expression pattern, prognostic significance, and potential roles of PLXND1 in HCC. We found that PLXND1 expression in HCC tissues was significantly higher compared with normal liver tissue from Gene Expression Profiling Interactive Analysis (GEPIA) and Integrative Molecular Database of Hepatocellular Carcinoma (HCCDB) databases. This result was further validated by immunohistochemistry staining (IHC) using tissue microarrays, which contained 216 HCC cases collected from our hospital. Additionally, PLXND1 expression showed a significant correlation with several clinical characteristics, including tumor grade and tumor hemorrhage (TH). Moreover, TISIDB and GEPIA databases were used to investigate the roles of PLXND1 in tumor-immune system interactions in HCC. As an immunoinhibitor, transforming growth factor-beta (TGF-β1) displayed the greatest correlations with PLXND1 in HCC. Finally, Kaplan-Meier curves and Cox analysis were conducted to further examine the potential clinical value of PLXND1 in HCC. We described a subclassification of HCC based on PLXND1 and TGF-β1 expression, which could be used to predict clinical outcomes and patient prognosis. Taken together, the results of this study indicate that PLXND1 might be a promising prognostic biomarker and potential therapeutic target in HCC.

Background. All YTH domain family members are m6A reader proteins accounting for the methylation modulation involved in the process of tumorgenesis and tumor progression. However, the expression profiles and roles of the YTH domain family in lung adenocarcinoma (LUAD) remain to be further illustrated. Methods. GEPIA2 and TNMplot databases were used to generate the expression profiles of the YTH family. Kaplan-Meier plotter database was employed to analysis the prognostic value of the YTH family. Coexpression profiles and genetic alterations analysis of the YTH family were undertaken using the cBioPortal database. YTH family protein-associated protein-protein interaction (PPI) network was identified by using STRING. Functional enrichment analysis was performed with the help of the WebGestalt database. The correlation analysis between the YTH family and immune cell infiltration in LUAD was administrated by using the TIMER2.0 database. Results. mRNA expression of YTHDC1 and YTHDC2 was significantly lower in LUAD, whereas YTHDF1, YTHDF2, and YTHDF3 with apparently higher expression. YTHDF2 expression was observed to be the highest in the nonsmoker subgroup, and its expression gradually decreased with the increased severity of smoking habit. LUAD patients with low expression of YTHDC2, YTHDF1, and YTHDF2 were correlated with a better overall survival (OS) time. The YTHDF1 genetic alteration rate was 26%, which was the highest in the YTH family. The major cancer-associated functions of YTH family pointed in the direction of immunomodulation, especially antigen processing and presentation. Most of the YTH family members were significantly correlated with the infiltration of CD4+ T cells, CD8+ T cells, macrophages, and neutrophils, indicating the deep involvement of the YTH domain family in the immune cell infiltration in LUAD. Conclusion. The molecular and expression profiles of the YTH family were dysregulated in LUAD. YTH family members (especially YTHDC2) were promising biomarkers and potential therapeutic targets that may bring benefit for the patients with LUAD.