The value of as prognostic and immunological biomarker in pan-cancer.

Background: Finding new immune-related biomarkers is one of the promising research directions for tumor immunotherapy. The gene could stimulate the WNT pathway and regulate the progression of various tumors. Recent studies have partially revealed the relationship between and tumor immunity, but the correlation and underlying mechanisms in pan-cancer remain obscure. Thus, we conducted this study aiming to characterize the prognostic value and immunological portrait of in cancer.

Methods: The data obtained from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Cancer Cell Line Encyclopedia (CCLE) databases was utilized to analyze expression levels by Kruskal-Wallis test and correlation to prognosis by Cox regression test and Kaplan-Meier test, while the data was also used to study the association between expression and immune microenvironment, immune neoantigens, immune checkpoints, tumor mutational burden (TMB), and microsatellite instability (MSI) in pan-cancer. Gene set enrichment analysis (GSEA) was used to clarify the relevant signaling pathways. The R package was used for data analysis and to create the plots.

Results: The pan-cancer analysis revealed that the expression level of is generally elevated in most tumors (19/34, 55.88%), and high expression was correlated with poor prognosis in esophageal carcinoma (ESCA, P<0.05), low-grade glioma (LGG, P<0.01), adrenocortical carcinoma (ACC, P<0.01), pancreatic adenocarcinoma (PAAD, P<0.01), and head and neck squamous cell carcinoma (HNSC, P<0.05). In addition, expression was positively associated with immune infiltration, stromal score, and immune checkpoints in most cancers, and correlated to immune neoantigens, TMB, and MSI. Finally, GSEA indicated that is implicated in the transforming growth factor β (TGFβ), Notch, and Hedgehog signaling pathways, which may be related to tumor immunity.

Conclusions: The expression of is elevated in most tumors and associated with tumor prognosis. Furthermore, is associated with tumor immunity and may be an immunological biomarker in cancer.