Long noncoding RNA, LINC00460, as a prognostic biomarker in head and neck squamous cell carcinoma (HNSCC)

Am J Transl Res. 2020 Feb 15;12(2):684-696. eCollection 2020.

Abstract

Head and neck squamous cell carcinoma (HNSCC) is an aggressive epithelial malignancy characterized by frequent mutations and metastasis. Long noncoding RNAs (lncRNAs) have been implicated in tumorigenesis and serve as novel prognostic biomarkers in different cancers. To enhance our understanding of lncRNAs that may have biological significance in HNSCC and may serve as prognostic biomarkers, we globally profiled lncRNAs in HNSCC by analyzing the RNA-seq data from The Atlas of Noncoding RNAs in Cancer (TANRIC) database. Of 3576 lncRNAs, we identified 926 (higher-688, lower-238) lncRNAs with a 2-fold abundance difference among the forty HNSCC and paired adjacent normal tissue. We investigated differential abundance of lncRNAs based on TP53 mutation and p16 status. We found 133 lncRNAs to have differential abundance by 2-fold among the mutant vs wild-type TP53 samples, whereas among p16-negative vs positive samples, we identified 710 lncRNAs with the same criteria. Meanwhile, analysis of the 15 most abundant lncRNAs in the tumor samples identified five lncRNAs whose higher abundance was associated with poor overall patient survival. Among these five, higher abundance of LINC00460 associated with poor patient survival in an independent cohort of 82 HNSCC patients. To further evaluate the potential function of LINC00460, we performed lncRNA-mRNAs co-expression analysis and found that higher abundance of LINC00460 associated with cancer-related biological pathways including EMT and other inflammatory response pathways. In summary, we report LINC00460 is more abundant in tumors compared to adjacent normal tissue and that it may serve as a potential prognostic biomarker in HNSCC.

Keywords: Head and neck squamous cell carcinoma (HNSCC); RNA-seq; human papillomavirus (HPV); long noncoding RNAs (lncRNA); prognostic biomarker.