Pairing a prognostic target with potential therapeutic strategy for head and neck cancer.
作者： Sze Min Lek , Ke Li , Qiu Xuan Tan , Nicholas B Shannon , Wai Har Ng
DOI: 10.1016/J.ORALONCOLOGY.2020.105035
关键词:
摘要: OBJECTIVES We have previously identified and validated a panel of molecular prognostic markers (ATP13A3, SSR3, ANO1) for Head Neck Squamous Cell Carcinoma (HNSCC). The aim this study was to investigate the consequence ATP13A3 dysregulation on signaling pathways, aid in formulating therapeutic strategy targeting ATP13A3-overexpressing HNSCC. MATERIALS AND METHODS Gene Set Enrichment Analysis (GSEA) performed HNSCC microarray expression data (Internal local dataset [n = 92], TCGA [n = 232], EMBL [n = 81]) identify pathways associated with high ATP13A3. Validation using immunohistochemistry (IHC) tissue microarrays (TMAs) head neck cancers (n = 333), staining phosphorylated Aurora kinase A (phospho-T288). Short interfering RNA used knockdown patient derived cell lines. Protein then assessed by immunoblotting. RESULTS GSEA pathway be (p = 0.026). also trend towards poor prognosis tumor aggressiveness (p = 0.086, 0.094, respectively). Furthermore, immunohistochemical results revealed significant association between activity (p < 0.001). Knockdown human lines showed decrease levels. CONCLUSION Tumors are activity. This suggests potential role inhibitors subset patients overexpression
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