Overexpression of WD repeat domain 5 associates with aggressive clinicopathological features and unfavorable prognosis in head neck squamous cell carcinoma

摘要

Background WD repeat domain 5 ( WDR 5), a core member of Mixed lineage leukemia ( MLL ) and SET 1 histone H3 lysine 4 (H3K4) methyltransferase complexes, is involved in multiple biological and pathological processes. Its deregulation in cancer and pro‐tumorigenic roles has been increasingly appreciated. However, the expression pattern of WDR 5 and its biological functions in head neck squamous cell carcinoma ( HNSCC ) have not been well established. Methods The expression of WDR 5 mRNA in HNSCC was determined by data mining and interrogation using publicly available databases. Its protein expression was measured by immunohistochemistry in a retrospective cohort of primary HNSCC samples. Moreover, the associations between WDR 5 expression and various clinicopathological parameters and patient survival were assessed. The pro‐tumorigenic roles of WDR 5 in HNSCC were further delineated in?vitro by loss‐of‐function assay. Results Our bioinformatics analyses revealed that WDR 5 mRNA was significantly overexpressed in 3 HNSCC cohorts. WDR 5 protein was markedly upregulated in HNSCC samples as compared to normal counterparts and its overexpression significantly associated with large tumor size, advanced clinical stage (chi‐square test, P? = ? .048, .006) and reduced overall and disease‐free survival (Kaplan‐Mier analyses, Log‐rank test, P? = ? .0137, .0154). Univariate and multivariate survival analyses further revealed WDR 5 protein abundance as an independent prognostic factor for patients’ overall survival. Moreover, WDR 5 knockdown significantly inhibited cell proliferation, migration and invasion, and induced cell apoptosis in HNSCC cells. Conclusions Our findings reveal that WDR 5 is aberrantly overexpressed in HNSCC and associates with aggressiveness and unfavorable prognosis, thus representing a novel diagnostic and prognostic biomarker for HNSCC .