Abstract 5406: Predictive value of tumor microRNAs in head and neck cancer patients treated with intensity-modulated radiation therapy
Authors: Ahmad Parwez , Sana Jiri , Vecera Marek , Juracek Jaroslav , Machackova Tana , Gablo Natalia Anna , Svoboda Marek , Hermanova Marketa , Slavik Marek , Slampa Pavel , Smilek Pavel , Slaby Ondrej 
Published: August 2018

Abstract
Introduction: Head and neck cancers are the sixth most common cancers worldwide mainly represented by the squamous cell carcinoma (HNSCC). Very important treatment modality in HNSCC is radiotherapy (RT). Closed as well as ongoing clinical trials are evaluating especially potential for reduced-dose RT in less aggressive radiosensitive HNSCC defined by human papillomavirus (HPV) positivity, with promise of less acute and late toxicity. To this end, variety of different biomarkers with promising predictive value is currently investigated in HNSCC. MicroRNAs (miRNAs) are short endogenous RNAs that post-transcriptionally modulate gene expression and their deregulated expression has been observed in many cancers including HNSCC. Specific expression patterns of miRNAs have been also shown to predict prognosis and therapeutic response in HNSCC. Aim of our study was to identify tumor tissue miRNAs enabling of predict locoregional control (LRC) in HNSCC patients who underwent intensity-modulated RT.
Materials and methods: We have analyzed global miRNA expression profiles in 43 FFPE tumor biopsies collected from HNSCC patients treated with intensity-modulated radiation therapy, who were divided into two groups according to their LRC as follows: short LRC [n = 22; median 5.1 months (min 1.3, max 18.6)] vs. long LRC [n = 21; 60.4 (46.8, 98.8)]. This analysis has been performed using the hybridization Affymetrix GeneChip miRNA 4.0 array. Validation of miRNA candidates was performed in independent cohort of 64 HNSCC patients. MiRNA determination was carried out by RT qPCR technology using the miRNA-specific RT stem-loop primers according to the Taq-Man MicroRNA Assay protocol (Thermo Fisher Scientific).
Results: We identified 24 miRNAs with significantly different expression between both examined groups (p &lt; 0.05; average log(Fold Change) = 0.42). Based on pre-defined critera, 12 miRNAs were selected for independent validation, from which miR-421 and miR-1228 were differentially expressed between groups of patients with short and long LRC. Moreover, risk-score based on combination of these 2 miRNAs expression and CD44 status enabled to predict 3-years LRC with 82% sensitivity and 82% specificity (AUC = 0.798).
Conclusion: Our results suggest that miR-421 and miR-1228 are promising predictive biomarkers in HNSCC patients treated with intensity-modulated RT. This work was supported by Ministry of Health of the Czech Republic, grant nr. 15-34553A, 15-33158A, 15-31627A, 15-34678A, 16-31314A and 16-31765A.
Citation Format: Parwez Ahmad, Jiri Sana, Marek Vecera, Jaroslav Juracek, Tana Machackova, Natalia Anna Gablo, Marek Svoboda, Marketa Hermanova, Marek Slavik, Pavel Slampa, Pavel Smilek, Ondrej Slaby. Predictive value of tumor microRNAs in head and neck cancer patients treated with intensity-modulated radiation therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5406.