Abstract
The mortality rate of head and neck squamous cell carcinoma (HNSCC), one of the most prevalent types of cancer, has remained unchanged despite advances in treatment strategies. Angiopoietin‑like 4 (ANGPTL4) exhibits both pro‑ and anti‑tumorigenic roles in various cancers depending on the tissue context. The present study investigated the role of ANGPTL4 expression in oropharyngeal squamous cell carcinoma (OPSCC). Data from 137 patients with OPSCC who underwent initial treatment were retrospectively analyzed. ANGPTL4 expression in tumor tissues was determined via immunohistochemistry. Survival outcomes [overall survival (OS) and disease‑free survival (DFS)] and clinicopathological correlations were evaluated. Tumor cell proliferation was assessed using an CellTiter‑Glo 2.0 luminescence‑based cell viability assay, immunofluorescence staining, and reverse transcription‑quantitative polymerase chain reaction following small interfering RNA‑mediated knockdown in a HNSCC cell line. Gene set enrichment analysis (GSEA) was performed using data from The Cancer Genome Atlas. ANGPTL4 expression (≥7.7%) in patients with OPSCC was significantly associated with improved OS and DFS. Multivariate analysis confirmed that low ANGPTL4 expression was an independent prognostic factor for OS [hazard ratio (HR)=3.676, 95% confidence interval (CI)=1.678‑8.056; P=0.001) and DFS (HR=2.959, 95% CI=1.533‑5.713; P=0.001)]. FaDu cells with ANGPTL4 knockdown demonstrated significantly increased proliferation compared with negative controls in the CellTiter‑Glo 2.0 assay (P=0.010), accompanied by a significant increase in Ki‑67 expression as revealed by immunofluorescence staining (P=0.021). The relative ANGPTL4 mRNA expression levels decreased to 38%, whereas those of MKI67 increased significantly. GSEA revealed significant enrichment of cell cycle progression signatures in cases with low ANGPTL4 expression. ANGPTL4 expression was significantly associated with a favorable prognosis in OPSCC, and its knockdown increased proliferative activity in FaDu cells. Thus, ANGPTL4 may serve as a prognostic biomarker in OPSCC. Further in vivo studies are warranted to clarify causality and assess the therapeutic potential of ANGPTL4 targeting in OPSCC.