Identification of HOXB9 based on comprehensive bioinformatics analysis for predicting prognosis of head and neck squamous cell carcinoma

Abstract

To evaluate the correlation between HOXB9 expression, and the prognosis and immune infiltration in head and neck squamous cell carcinoma (HNSCC). Pan-cancer HOXB9 expression was analyzed through TIMER2.0. The HOXB9 expression data of HNSCC and normal tissues were compared using the gene expression profiling interactive analysis (GEPIA) and the cancer genome atlas (TCGA) databases. The University of Alabama at Birmingham (UALCAN) database was used to analyze the relative expression of HOXB9 in HNSCC subgroups based on clinicopathological features, including cancer stage, tumor grade and lymph node stage. Survival analysis was performed using GEPIA, TCGA-Portal, Kaplan–Meier Plotter, and UALCAN databases. The genes co-expressed with HOXB9 were identified using TCGA data, and functionally annotated by GO and KEGG analyses. Protein-protein interaction network was constructed using the STRING database and Cytoscape 3.7.1. Single-sample gene set enrichment analysis was performed to assess the correlation between HOXB9 and immune infiltration based on TCGA data. TIMER 2.0 database was used to explore the correlation between HOXB9 expression and immune infiltration multiple cancers. HOXB9 mRNA is elevated in multiple cancers, and was upregulated in HNSCC tissues compared to non-paired (P < .05 in GEPIA; P < .0001 in TCGA) as well as paired (P < .0001 in TCGA) normal tissues. In addition, HOXB9 expression was positively correlated with tumor malignancy in the GEPIA and UALCAN databases (P < .05), and negatively with patient prognosis in both databases (P < .05). High HOXB9 expression was associated with increased infiltration of aDCs, NK CD56bright cells, NK cells, and Th2 cells (P < .05), while low HOXB9 expression was associated with an increase in the proportion of DCs, iDCs, mast cells, neutrophils, and Th17 cells (P < .05). HOXB9 likely functions as an oncogene in HNSCC by disrupting the immune landscape, and is a promising prognostic biomarker and therapeutic target.