Abstract 151: Transcriptome-wide expression profiling of long noncoding and small nucleolar RNAs in head and neck squamous cell carcinomas identifies novel transcripts associated with survival

Abstract

Abstract Head and neck squamous cell carcinoma (HNSCC) persists as one of the most common and deadly malignancies, with early detection and effective treatment still posing formidable challenges. To expand our currently sparse knowledge of the epigenetic alterations involved in this disease and identify potential biomarkers and therapeutic targets, we globally profiled the dysregulation of small nucleolar (snoRNA) and long non-coding RNAs (lncRNA) in head and neck tumors. Using next-generation RNA-sequencing data from 40 pairs of tumor and matched normal tissues, we profiled lncRNA expression by mapping each RNA-seq library to a reference annotation containing 32,108 lncRNAs. Using edgeR, we found 19,681 lncRNA transcripts significantly differentially expressed by a fold change magnitude ≥ 4 with a false discovery rate <10-4. We selected the 10 most dysregulated lncRNAs and further confirmed the dysregulation of these lncRNAs in-vitro by performing quantitative reverse transcriptase PCR (RT-qPCR) on two normal oral epithelial cell lines and five HNSCC cell lines. Using Kaplan-Meier analysis, we demonstrated a correlation between high expression of several lncRNAs, including JPH1-7, upregulated by 40-fold in HNSCC, with overall poor survival in a cohort of over 400 HNSCC patients (HR = 1.62, p < 0.01). Meanwhile, RNA-sequencing analysis of 31 tumor-normal pairs yielded 33 significantly dysregulated snoRNA. We identified one snoRNA, SNORD116-20, downregulated by 4-fold in HNSCC, whose expression levels correlated significantly with overall patient survival (HR = 1.64, p < 0.05), suggesting its functional significance and clinical relevance in head and neck cancer pathogenesis. Similarly, in in-vitro experiments, we found reduced expression of this snoRNA in HNSCC cell lines compared to normal oral epithelial cell lines. The precise molecular roles of these transcripts identified warrants further characterization, but our data suggest that they are likely to play substantial roles in head and neck cancer pathogenesis and are significantly associated with patient survival. Note: This abstract was not presented at the meeting. Citation Format: Thomas K. Honda, Angela Zou, Vicky Yu, Hao Zheng, Selena Kuo, Maarouf Saad, Yinan Xuan, Pranav Singh, Jessica Wang-Rodriguez, Weg M. Ongkeko. Transcriptome-wide expression profiling of long noncoding and small nucleolar RNAs in head and neck squamous cell carcinomas identifies novel transcripts associated with survival. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 151. doi:10.1158/1538-7445.AM2015-151