Pan-cancer analysis of HAVCR2 based on machine learning: A potential target of survival and immunotherapy

Hepatitis A virus cellular receptor 2 (HAVCR2) is an immune checkpoint inhibitor, whose expression is closely associated with tumor exhaustion. However, there is no systemic pan-cancer analysis of HAVCR2. Our study aims to understand its multi-omics profiles, genetic alterations, prognostic significance, biological functions, immune infiltration patterns, and the relationship with drug sensitivity using multi-omics bioinformatics from public databases. HAVCR2 was significantly upregulated in 24 types of cancers and associated with prognosis, as indicated by a comprehensively integrated analysis of The Cancer Genome Atlas and Genotype-Tissue Expression portals. The DNA methylation and protein levels of HAVCR2 were also assessed in pan-cancer by UALCAN and CPTAC. Besides, high HAVCR2 expression group in different cancers was associated with worse or better prognosis for overall survival and disease-free survival. Further, pathways involved in HAVCR2 were all associated with human immunity. Then, HAVCR2 expression exhibited significantly and positively correlated with DCs, CD4+ T cells, neutrophils, and macrophages in most cancers, but had almost no correlation with all immune cells in some cancers, which might mean that HAVCR2 hardly affects the immune microenvironment of these cancers. Besides, HAVCR2 was positively correlated with most known immunomodulatory genes, especially CCR1, CCR5, PDCD1LG2, and CD86. Totally, our work provided new insights and theoretical basis for HAVCR2 as a drug target.