Systematic Analysis and Identification of Dysregulated Panel lncRNAs Contributing to Poor Prognosis in Head-Neck Cancer.

Shang-Ju Tang,Joseph T Chang,Guo-Rong You,Ann-Joy Cheng

doi:10.3389/fonc.2021.731752

Shang-Ju Tang, Joseph T Chang + Show 2 more

Open Access

https://doi.org/10.3389/fonc.2021.731752

Copy DOI

Abstract

Head and neck cancer (HNC) is one of the most prevalent cancers worldwide, accounting for approximately 5% of all cancers. While the underlying molecules and their pathogenetic mechanisms in HNC have yet to be well elucidated, recent studies have shown that dysregulation of lncRNAs may disrupt the homeostasis of various biological pathways. However, the understanding of lncRNAs in HNC is still limited by the lack of expression profiling. In the present study, we employed a systematic strategy to identify a panel of lncRNA associated with HNC. A cancer-related lncRNA profile PCR array was screened to explore potential molecules specific for HNC. A total of 55 lncRNAs were found to be dysregulated in HNC cells when compared to normal keratinocytes. Further analysis of the prognostic significance using The Cancer Genome Atlas (TCGA) database revealed 15 lncRNAs highly correlated with overall survival in HNC patients. Additionally, clinical sample expression analysis of the TCGA-HNSC cohort revealed 16 highly dysregulated lncRNAs in HNC, resulting in a combined 31-lncRNA signature panel that could predict prognosis. Validation of these molecules confirmed the considerable level of altered expressions in HNC cells, with XIST, HOXA11-AS, TSIX, MALAT1, WT1-AS, and IPW being the most prominently dysregulated. We further selected a molecule from our panel (XIST) to confirm the validity of these lncRNAs in the regulation of cancer aggressiveness. Gene ontology (GO) and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analyses demonstrated that XIST participated in various cancer-related functions, including cell proliferation and metastasis. XIST silencing with the RNAi technique substantially reduced invasion and migration in several HNC cell lines. Thus, our study defined a 31-lncRNA panel as prognostic signatures in HNC. These perspective results provide a knowledge foundation for further application of these molecules in precision medicine.

Highlights

Head and neck cancer (HNC) is a complex and difficult to treat disease
To profile lncRNAs associated with HNC, a PCR array with 84 cancer-related lncRNAs was used to examine the differential expressions between three HNC cell lines (SAS, OECM1, and FaDu) and two lines of normal keratinocytes (CGHNK2 and CGHNK6)
Hierarchical clustering analysis was used to visualize these differentially expressed lncRNAs (Figure 1C). These results suggest a panel candidate of lncRNA that may participate in the carcinogenesis of HNC

Summary

Introduction

Head and neck cancer (HNC) is a complex and difficult to treat disease. While this type of cancer encompasses dysregulations at areas including the mouth, nasal cavity, larynx, and pharynx, over 90% of all HNCs are squamous cell carcinomas, and of the oral region [1]. Together, they account for approximately 5% of all cancers worldwide, according to GLOBOCAN 2020 estimates [2]. Standard treatment methods include surgery, radiotherapy, chemotherapy, or combination therapy [3]. It is critical to identify and understand how these carcinogenic mechanisms and molecules affect cancer, as we may be able to uncover the mysteries behind HNC and how to treat and/or prevent it

Methods

Results

Conclusion