PO-366 Long non-coding RNAs TINCR and DANCR in urothelial carcinoma subtypes

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Introduction Long non-coding RNAs (lncRNAs) are a diverse set of transcripts spanning more than 200 nucleotides. Many show a tissue-specific expression pattern and are involved in fine tuning of cell fate determination by regulating gene expression. Two lncRNAs, TINCR and DANCR, are known as important factors in keratinocyte differentiation. Upregulation of TINCR is required for terminal epidermal differentiation whereas DANCR maintains the undifferentiated state of keratinocytes. We wondered whether these lncRNAs could be involved in aberrant differentiation of urothelial carcinoma (UC) and contribute to the development a specific molecular UC subtypes with squamous features, termed Basal-Squamous-like-subtype (BASQ). We analysed lncRNA expression in a large set of UC tissues and a smaller set of bladder squamous cell carcinomas (B-SCC) and compared the results with TCGA RNA-Seq data. Material and methods LncRNA expression was measured by qRT-PCR in 161 UC, 8 normal and 12 B-SCC samples. RNA-Seq data from the TCGA cohort was accessed via the TANRIC database. Statistical comparison for differential expression between each group was done by Wilcoxon rank sum test in R. Correlation of histopathological patient data with lncRNA expression was performed using SPSS. The Broad institute Morpheus tool was used for hierachical cluster analysis of the TCGA RNA-Seq data to identify associations of lncRNA expression with UC molecular subtypes. Results and discussions Consistent with the TCGA RNA-Seq data, qRT-PCR analysis of our large tissue set revealed both TINCR and DANCR to be upregulated in UC and in B-SCC compared to benign tissues. According to the qRT-PCR data, DANCR expression was significantly elevated in non-invasive over invasive tumours. Kaplan-Meier analysis did not reveal associations of patient outcome with upregulated lncRNA expression, except that high TINCR expression was associated with worse metastasis-free survival. Hierarchical cluster analysis indicated that the BASQ subtype, which is defined by low expression of luminal marker genes (FOXA1, GATA3) and high expression of basal and squamous marker genes (KRT5, KRT6, KRT14), is also characterised by intermediate TINCR expression. Conclusion Both TINCR and DANCR expression are frequently upregulated in UC, but are not strongly associated with clinical parameters. Instead, our data support the emerging consensus that specific lncRNA expression patterns are associated with and may contribute to the characteristics of UC molecular subtypes.