Abstract 3583: Differential expression of noncoding RNAs in black compared with white laryngeal cancers
Authors: Fredenburg Kristianna , Jiang Jinmai , Schmittgen Tom 
Published: August 2019

Background: Compared with other races, Blacks have maintained a higher incidence, prevalence, and poorer survival for laryngeal squamous cell carcinoma (LSCC). To date, a molecular basis remains undefined. Noncoding RNAs (ncRNAs), in particular microRNAs, have been found to be dysregulated in cancers with disparate outcomes. Ultraconserved RNAs (UCR), a highly conserved, new class of ncRNA, are regulated by miRNAs and differentially expressed in cancer. No studies to date have explored the dysregulation of these elements in Black compared with White LSCC. We present, here, our miRNA and UCR data from Black LSCC, White LSCC, and normal mucosal tissues.

Methods: RNA was isolated from 32 fresh frozen tumors (16 Black and 16 White) and normal mucosal tissues (10 White and 1 Black). For miRNA analysis, small RNA library construction and sequencing were performed. Differentially expressed miRNAs identified through sequencing were considered for qPCR validation using the criteria of FDR &lt;0.05, FC &gt;1.5. The expression of 481 transcribed-UCRs (T-UCR) was profiled using primers designed to each T-UCRs. A T-UCR was considered expressed in a particular sample if the mean CT ≤ 35. miRNAs and T-UCR were considered differentially expressed if the fold change between the comparative groups was greater than 1.5-fold and p &lt; 0.05 (FDR).

Results: Our data show that there are significant differences in the somatic expression of two miRNAs, miR-9-5p and miR-191-5p, where both miRNAs were decreased in Black LSCC compared with White. However, when compared to normal mucosa, miR-9-5p was significantly overexpressed only in White LSCCs not in Black. In contrast, miR-191-5p was significantly decreased in Black LSCC compared to normal mucosa but not in White. This trend was seen also in our T-UCR data, where compared to normal mucosa, uc.424 was significantly overexpressed only in Black LSCC whereas uc.401 and uc.012 were significantly overexpressed only in White LSCC. Overall comparison of tumor to normal mucosa revealed 4 T-UCRs, uc.401, uc.389, uc.382, uc.218 were overexpressed in tumor compared to normal. No differences in T-UCR expression was identified in Black LSCC compared to White LSCC.

Conclusions: In summary, our data show that there are somatic expression differences and baseline expression differences in ncRNAs between Black and White LSCC. Our data suggest that gene regulatory mechanisms may differ in Black and White LSCC. Additionally, we are the first to identify T-UCR expression differences in laryngeal cancer. Through their interplay with miRNAs, these elements may contribute to LSCC tumorigenesis. Future studies will focus on uncovering the functional consequences of our differentially expressed ncRNAs and determining the manner in which they impact disparate outcomes seen in LSCC.

Citation Format: Kristianna Fredenburg, Jinmai Jiang, Tom Schmittgen. Differential expression of noncoding RNAs in black compared with white laryngeal cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3583.