Pairing a prognostic target with potential therapeutic strategy for head and neck cancer
| Autor: | Oi Lian Kon, Nicholas B. Shannon, Ke Li, Gerald Tay, Yudong Chen, Hiang Khoon Tan, N. Gopalakrishna Iyer, Jacqueline S.G. Hwang, Daniel Shao-Weng Tan, Khee Chee Soo, Chin-Ann Johnny Ong, Sze Min Lek, Josephine Hendrikson, Tony Kiat Hon Lim, Fui Teen Chong, Qiu Xuan Tan, Mei Kim Ang, Hui Jun Lim, Natascha Putri, Hui Sun Leong, Kelvin K.N. Koh, Xue Lin Kwang, Thakshayeni Skanthakumar, Ngian Chye Tan, Wai Har Ng, Joey W. S. Tan |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Cancer Research Microarray Aurora A kinase 03 medical and health sciences 0302 clinical medicine Aurora kinase Cell Line Tumor Humans Medicine Gene Silencing Molecular Targeted Therapy RNA Small Interfering 030223 otorhinolaryngology Protein Kinase Inhibitors Aurora Kinase A Adenosine Triphosphatases Gene knockdown Tissue microarray Squamous Cell Carcinoma of Head and Neck business.industry Membrane Transport Proteins Prognosis medicine.disease Immunohistochemistry Head and neck squamous-cell carcinoma Oncology Head and Neck Neoplasms Tissue Array Analysis 030220 oncology & carcinogenesis Cancer research Female Oral Surgery business Signal Transduction |
| Zdroj: | Oral Oncology. 111:105035 |
| ISSN: | 1368-8375 |
| Popis: | OBJECTIVES We have previously identified and validated a panel of molecular prognostic markers (ATP13A3, SSR3, and ANO1) for Head and Neck Squamous Cell Carcinoma (HNSCC). The aim of this study was to investigate the consequence of ATP13A3 dysregulation on signaling pathways, to aid in formulating a therapeutic strategy targeting ATP13A3-overexpressing HNSCC. MATERIALS AND METHODS Gene Set Enrichment Analysis (GSEA) was performed on HNSCC microarray expression data (Internal local dataset [n = 92], TCGA [n = 232], EMBL [n = 81]) to identify pathways associated with high expression of ATP13A3. Validation was performed using immunohistochemistry (IHC) on tissue microarrays (TMAs) of head and neck cancers (n = 333), staining for ATP13A3 and phosphorylated Aurora kinase A (phospho-T288). Short interfering RNA was used to knockdown ATP13A3 expression in patient derived HNSCC cell lines. Protein expression of ATP13A3 and Aurora kinase A was then assessed by immunoblotting. RESULTS GSEA identified Aurora kinase pathway to be associated with high expression of ATP13A3 (p = 0.026). The Aurora kinase pathway was also associated with a trend towards poor prognosis and tumor aggressiveness (p = 0.086, 0.094, respectively). Furthermore, the immunohistochemical staining results revealed a significant association between Aurora kinase activity and high ATP13A3 expression (p |
| Databáze: | OpenAIRE |
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