The overexpression of HOXC6 in LUSC and pan-squamous cell carcinomas indicates the coexistence of nuclear division regulatory mechanisms

BackgroundHomeobox C6 (HOXC6) shows abnormal expression in various tumors, but its pattern in lung squamous cell carcinoma (LUSC) remains unclear.ObjectiveTo investigate HOXC6's expression and function in LUSC.MethodsHOXC6 expression was analyzed using single-cell RNA sequencing (scRNA-seq) in LUSC, cervical squamous cell carcinoma (CESC), esophageal squamous cell carcinoma (ESCC), laryngeal squamous cell carcinoma (LSCC), and oral squamous cell carcinoma (OSCC), verified by RNA-seq and immunohistochemistry (IHC). CRISPR knockdown assessed proliferation impact. Immune infiltration analysis, single-sample Gene Set Enrichment Analysis (ssGSEA), Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses explored immune microenvironment relationships.ResultsHOXC6 was highly expressed in LUSC (standard mean difference (SMD) = 1.17, confidence interval (CI) = 0.75-1.59, area under the curve (AUC) = 0.88), confirmed by IHC (P = 1.6e-10, AUC = 0.99). HOXC6 silencing inhibited proliferation. High expression negatively correlated with immune infiltration and decreased StromalScore, ImmuneScore, and ESTIMATEScore. HOXC6 was elevated in other squamous carcinomas.ConclusionHigh HOXC6 expression may promote LUSC and pan-squamous carcinoma development through mitosis regulation.