Head and neck squamous cell carcinoma (HNSCC) is an aggressive disease marked by frequent recurrence and metastasis and stagnant survival rates. To enhance molecular knowledge of HNSCC and define a non-coding RNA (ncRNA) landscape of the disease, researchers at UCSD profiled the transcriptome-wide dysregulation of long non-coding RNA (lncRNA), microRNA (miRNA), and PIWI-interacting RNA (piRNA) using RNA sequencing data from 422 HNSCC patients in The Cancer Genome Atlas (TCGA). 307non-coding transcripts differentially expressed in HNSCC were significantly correlated with patient survival, and associated with mutations in TP53, CDKN2A, CASP8, PRDM9,and FBXW7 and copy number variations in chromosomes 3, 5, 7, and 18. The researchers also observed widespread ncRNA correlation to concurrent TP53 and chromosome 3p loss, a compelling predictor of poor prognosis in HNSCCs. Three selected ncRNAs were additionally associated with tumor stage, HPV status, and other clinical characteristics, and modulation of their expression in vitro reveals differential regulation of genes involved in epithelial-mesenchymal transition and apoptotic response. This comprehensive characterization of the HNSCC non-coding transcriptome introduces new layers of understanding for the disease, and nominates a novel panel of transcripts with potential utility as prognostic markers or therapeutic targets.
Heatmaps of significantly differentially expressed non-coding RNAs in HNSCC
(A) Heatmap depicting normalized expression levels (in counts-per-million) of the 100 lincRNA transcripts with the largest magnitude of dysregulation in HNSCCs compared to paired normal samples (FDR < 0.0001). Inset highlights the 4 experimentally validated isoforms of lnc-JPH1-7. (B) Expression plot of lnc-JPH1-7 in HNSCCs compared to adjacent normal tissue. (C–D) Heatmaps depicting normalized expression levels (in counts-permillion) of (D) 232 miRNAs (FDR < 0.05) and (E) 61 piRNAs (FDR < 0.05) dysregulated in HNSCC tumors, highlighting discussed or ultimately experimentally validated transcripts.