Abstract
Cisplatin is an important drug for the treatment of head and neck squamous cell carcinoma (HNSCC). Determining chemoresistant factors prior to treatment will lead to great benefits for clinicians and patients. Here, we evaluated chemoresistant factors by integrating proteomic and transcriptomic data using HNSCC cell lines to identify a more precise chemoresistant factor in HNSCC. We used four HNSCC cell lines: cisplatin-sensitive, acquired cisplatin resistance, naturally cisplatin-resistant, and acquired 5-FU resistance. Proteomic analysis was performed using iTRAQ, tandem mass spectrometry, and liquid chromatography-electrospray ionization-tandem mass spectrometry. Transcriptomic analysis was performed using microarrays. By integrating these independent data, common factors were addressed and functional analysis was performed using small interfering RNAs (siRNAs) to change the chemosensitivity. Using iTRAQ analysis, 7 proteins were identified as specific for cisplatin chemoresistance factors. Transcriptomic analysis revealed hundreds of potential candidate factors. By combining and integrating these data, S100A2 was identified as a potential cisplatin-specific chemoresistance factor. Functional analysis with siRNA revealed that the expression of S100A2 was reduced and cisplatin sensitivity recovered in the acquired and naturally cisplatin-resistant cell lines, but not in the cisplatin-sensitive cell lines. S100A2 was identified as a cisplatin-specific chemoresistance factor by integrating the transcriptomic and proteomic results obtained using HNSCC cell lines. This is a novel technique that allows for a precise identification, also known as a comprehensive analysis. Our findings indicate that these proteins could be used as biomarkers of HNSCC treatments, providing physicians with new treatment strategies for patients with HNSCC, showing chemoresistance.