A pan-cancer analysis of the role of HOXD1, HOXD3, and HOXD4 and validation in renal cell carcinoma

HOXD1, HOXD3, and HOXD4 are members of the HOXD genes family and are related to tumorigenesis of the tumor. However, whether HOXDs (1, 3, 4) have a crucial role across pan-cancer is still unknown. HOXD1, HOXD3, and HOXD4 expressions were analyzed using public databases in 33 types of tumors. The UCSC Xena website was carried out to investigate the relationship between the expression of genes and the progress of cancers. The biological functions of HOXD3 were tested by colony forming, transwell, wound healing, and xenograft assay in vitro and in vivo. GSEA was used to identify the associated cancer hallmarks with HOXDs expression. Immune cell infiltration analysis was applied to verify the immune cell infiltrations related to genes. The results showed HOXD1, HOXD3, and HOXD4 co-low expressed in BRCA, COAD, KICH, KIRC, KIRP, READ, and TGCT. In the KIRC, all of HOXDs expression was connected with tumor stage and histological grade. Upregulation of HOXDs was associated with improved OS, DSS, and PFI. Down-expression of HOXD3 induced cell proliferation, migration, and invasion in vivo and in vitro. In addition, HOXDs were connected with immune-activated hallmarks and cancer immune cell infiltrations. These findings demonstrated that HOXDs may be indicative biomarkers for the prognosis and immunotherapy in pan-cancer.