Abstract
The homeobox A cluster (HOXA) gene family, comprising 11 members, is involved in a wide spectrum of biological functions in human cancers. However, there is little research on the expression profile and prognostic values of HOXA genes in laryngeal squamous cell cancer (LSCC). Based on updated public resources and integrative bioinformatics analysis, we assessed the expression profile and prognostic values of the HOXA family members. Expression and methylation data on HOXA family members were obtained from The Cancer Genome Atlas (TCGA). The prognostic values of HOXA members and clinical features were identified. A gene set enrichment analysis (GSEA) was conducted to explore the mechanism underlying the involvement of HOXA members in LSCC. The associations between tumor immune infiltrating cells (TIICs) and the HOXA family members were evaluated using the Tumor Immune Estimation Resource (TIMER) database. HOXA2 and HOXA4 were downregulated and HOXA7 and HOXA9–13 were upregulated in LSCC. Upregulation of HOXA10, HOXA11, and HOXA13, along with two clinical characteristics (M stage and gender), were associated with a poor LSCC prognosis based on the results of univariate and multivariate Cox proportional hazards regression analyses. Although there were no significant correlations between TIICs and HOXA members, the GSEA results indicated that HOXA members participate in multiple biological processes underlying tumorigenesis. This study comprehensively analyzed the HOXA members, providing insights for further investigation of the HOXA family members as potential targets in LSCC.
Highlights
Laryngeal cancer is one of the most common malignancies in the head and neck region, and laryngeal squamous cell cancer (LSCC) accounts for more than 95% of cases [1]
The mRNA expression data on homeobox A cluster (HOXA) members (HOXA1–13) from 111 LSCC samples and 12 normal control samples, which originated from The Cancer Genome Atlas (TCGA), were obtained using Perl software
There were no significant differences in HOXA1, HOXA3, HOXA5, and HOXA6 expression between LSCC and control tissues
Summary
Laryngeal cancer is one of the most common malignancies in the head and neck region, and laryngeal squamous cell cancer (LSCC) accounts for more than 95% of cases [1]. Despite progress regarding comprehensive therapeutic strategies to treat LSCC, the prognosis of LSCC remains unsatisfactory, as 30–40% of patients die within 5 years of diagnosis with advanced LSCC [2]. Identification of reliable biomarkers for LSCC prognosis could facilitate individualized treatment. The HOX gene family is one of the families of homeobox genes that function as developmental regulatory genes [3]. There are 39 HOX genes in four gene clusters named HOXA, HOXB, HOXC, and HOXD [4]. The HOXA cluster comprises 11 genes (including HOXA1, HOXA2, HOXA3, HOXA4, HOXA5, HOXA6, HOXA7, HOXA9, HOXA10, HOXA11, and HOXA13), which
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