Unraveling the oral cancer lncRNAome: Identification of novel lncRNAs associated with malignant progression and HPV infection

Abstract

Objectives The role of long non-coding RNA (lncRNA) expression in human head and neck squamous cell carcinoma (HNSCC) is still poorly understood. In this study, we aimed at establishing the onco-lncRNAome profiling of HNSCC and to identify lncRNAs correlating with prognosis and patient survival. Materials and Methods The Atlas of Noncoding RNAs in Cancer (TANRIC) database was employed to retrieve the lncRNA expression information generated from The Cancer Genome Atlas (TCGA) HNSCC RNA-sequencing data. RNA-sequencing data from HNSCC cell lines were also considered for this study. Bioinformatics approaches, such as differential gene expression analysis, survival analysis, principal component analysis, and Co-LncRNA enrichment analysis were performed. Results Using TCGA HNSCC RNA-sequencing data from 426 HNSCC and 42 adjacent normal tissues, we found 728 lncRNA transcripts significantly and differentially expressed in HNSCC. Among the 728 lncRNAs, 55 lncRNAs were significantly associated with poor prognosis, such as overall survival and/or disease-free survival. Next, we found 140 lncRNA transcripts significantly and differentially expressed between Human Papilloma Virus (HPV) positive tumors and HPV negative tumors. Thirty lncRNA transcripts were differentially expressed between TP53 mutated and TP53 wild type tumors. Co-LncRNA analysis suggested that protein-coding genes that are co-expressed with these deregulated lncRNAs might be involved in cancer associated molecular events. With consideration of differential expression of lncRNAs in a HNSCC cell lines panel (n=22), we found several lncRNAs that may represent potential targets for diagnosis, therapy and prevention of HNSCC. Conclusion LncRNAs profiling could provide novel insights into the potential mechanisms of HNSCC oncogenesis.

Long intergenic non-coding RNA 271 is predictive of a poorer prognosis of papillary thyroid cancer

“…edu/). Paired LINC00271 expression data in tumor and normal tissues were retrieved from TCGA RNA-sequencing data of PTC, BRCA, LUAD, KIRP, HNSCC, LIHC and PRAD by employing The Atlas of Noncoding RNAs in Cancer (TANRIC)33 (http://ibl.mdanderson.org/tanric/design/basic/index.html) and Gene Expression Omnibus data with accession number GSE3557036 (https://www.ncbi.nlm.nih.gov/geo/). …”

Differential expression and prognostic value of long non‐coding RNA in HPV‐negative head and neck squamous cell carcinoma

“…There is increasing evidence that aberrant expression of lncRNA plays a role in the genesis and progression of HNSCC . Through our present study, we were able to identify and validate 5 differentially expressed lncRNA in HPV‐negative HNSCC ( SPRY4‐IT1 , HEIH , LUCAT1 , LINC00152 , and HAND2‐AS1 ).…”

“…There is increasing evidence that aberrant expression of lncRNA plays a role in the genesis and progression of HNSCC. 24,25 Through our present study, we were able to identify and validate 5 differentially expressed lncRNA in HPV-negative HNSCC (SPRY4-IT1, HEIH, LUCAT1, LINC00152, and HAND2-AS1). Further, we found that low expression of MEG3 was associated with more favorable 3- year RFS, although the significance of this finding is unclear.…”

Clusterization in head and neck squamous carcinomas based on lncRNA expression: molecular and clinical correlates

“…5b). Interestingly, 4 lncRNA genes from c1 and 10 from c2 have been shown to be overexpressed in the larynx (Additional file 1: Table S6) [20]. Finally, we found that c1 patients are younger than the remaining patients (58.2 versus 61.6 years, p val = 0.018 after T test), and c2 patients older (65 versus 60.2 years, p val = 0.001 after T test) (Fig.…”

“…Interestingly, 16 out of 245 lncRNAs in cluster c5, depleted in TP53 mutations (Fig. 2c, d), have been shown to be overexpressed in TP53 wild type HNSCC samples [20]. In addition, 12 out of 245 c5 lncRNA genes were found upregulated in HPV-infected samples [20], in line with high frequency of HPV-positive samples in this cluster (Fig.…”