Abstract 1812: LncRNAs as prognostic biomarkers in head and neck squamous cell carcinoma (HNSCC)

Abstract

Abstract Long noncoding RNAs (lncRNAs) are transcripts that are greater than 200 nucleotides in length and do not encode proteins in contrast to mRNAs. They regulate a variety of cellular processes including cell proliferation and metastasis, and they have a role in cancer development. To identify lncRNAs that may have biological significance in head and neck squamous cell carcinoma (HNSCC), we globally profiled dysregulated lncRNAs in HNSCC. We analyzed RNA-seq data from HNSCC and paired adjacent normal tissue obtained from The Atlas of Noncoding RNAs in Cancer (TANRIC) database. Of 3576 lncRNAs, we identified 927 lncRNAs to be significantly (FDR <0.05) and differentially regulated by 2-fold among the HNSCC samples (upregulated-688, downregulated-239). Next, to evaluate the potential function of the lncRNAs, we performed lncRNA-mRNAs co-expression analysis for the top 10 upregulated lncRNAs and found that three of the lncRNAs (LINC01614, LINC02081, and LINC00460) are associated with cancer-related biological pathways including extracellular matrix organization, cell adhesion, and collagen catabolism. TP53 mutation status and presence of human papillomavirus (HPV) have been frequently associated with the survival in HNSCC. Therefore, we investigated differential expression of lncRNAs in 426 HNSCC based on TP53 mutation and HPV status. We identified 135 lncRNAs (upregulated-105, downregulated-30) to be significantly (FDR <0.05) and differentially regulated by 2-fold among the mutant vs wild-type TP53 samples. Among HPV-negative vs positive samples, we identified 714 differentially regulated lncRNAs (upregulated-203, downregulated-511). Interestingly, we found that LINC01614, LINC02081, and LINC00460 were also upregulated in mutant TP53 and HPV-negative HNSCC compared to wild-type TP53 and HPV-positive HNSCC. Survival analysis of the HNSCC patient data revealed that higher expression of LINC01614, LINC02081, and LINC00460 were significantly associated with poor overall survival. In addition, we were able to validate that higher expression of LINC02081 and LINC00460 were associated with poor overall survival in an independent data of 130 HNSCC generated at Moffitt Cancer Center. In summary, we identified lncRNAs that are differentially expressed in HNSCC compared to the normal tissue and may have a role in cancer development and metastasis pathways. LINC02081 and LINC00460 lncRNAs are associated with poor prognosis. Further evaluation of these lncRNAs is warranted to understand the mechanism and to potentially develop prognostic biomarkers in HNSCC. Citation Format: Ritu Chaudhary, Xuefeng Wang, Biwei Cao, Nicholas T. Gimbrone, Robbert JC Slebos, Christine H. Chung. LncRNAs as prognostic biomarkers in head and neck squamous cell carcinoma (HNSCC) [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 1812.