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Abstract
Increasing evidence has demonstrated the crosstalk between DNA epigenetic alterations and aberrant expression of long non-coding RNAs (lncRNAs) during carcinogenesis. However, epigenetically dysregulated lncRNAs and their functional and clinical roles in Head and Neck Squamous Cell Carcinoma (HNSCC) are still not explored. In this study, we performed an integrative analysis of DNA methylation data and transcriptome data and identified a DNA methylation-dysregulated four-lncRNA signature (DNAMeFourLncSig) from 596 DNA methylation-dysregulated lncRNAs using a machine-learning-based feature selection method, which classified the patients of the discovery cohort into two risk groups with significantly different survival including overall survival, disease-specific survival, and progression-free survival. Then the DNAMeFourLncSig was implemented to another two HNSCC patient cohorts and showed similar prognostic values in both. Results from multivariable Cox regression analysis revealed that the DNAMeFourLncSig might be an independent prognostic factor. Furthermore, the DNAMeFourLncSig was substantially correlated with the complete response rate of chemotherapy and may predict chemotherapy response. Functional in silico analysis found that DNAMeFourLncSig-related mRNAs were mainly enriched in cell differentiation, tissue development and immune-related pathways. Overall, our study will improve our understanding of underlying transcriptional and epigenetic mechanisms in HNSCC carcinogenesis and provided a new potential biomarker for the prognosis of patients with HNSCC.
Highlights
Head and neck squamous cell carcinoma (HNSCC) represents a heterogeneous group of malignancies derived from the oral cavity, larynx and pharynx, and has become the sixth most common cancer worldwide (Johnson et al, 2020)
Head and Neck Squamous Cell Carcinoma (HNSCC) is an aggressive, life-threatening disease associated with low survival rates because of the failure of early diagnosis
We performed an integrative analysis of DNA methylation data and transcriptome data to explore the relationship between epigenetic alterations and Long non-coding RNAs (lncRNAs) expression, as well as their prognostic value in HNSCC
Summary
Head and neck squamous cell carcinoma (HNSCC) represents a heterogeneous group of malignancies derived from the oral cavity, larynx and pharynx, and has become the sixth most common cancer worldwide (Johnson et al, 2020). Increasing evidence and studies have demonstrated the widespread dysregulation of lncRNAs in many human diseases, including cancers (Fang and Fullwood, 2016). These dysregulated lncRNAs play essential roles in cancer development, progression, metastasis and therapy, have widely been recognized as potential attractive biomarkers and therapeutic targets (Jiang M.C. et al, 2019; Bao et al, 2020; Sun et al, 2020; Yan et al, 2020; Zhou et al, 2020). We performed an integrative analysis of DNA methylation data and transcriptome data to explore the relationship between epigenetic alterations and lncRNAs expression, as well as their prognostic value in HNSCC
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