Identification of Molecular Subtypes in Head and Neck Squamous Cell Carcinoma Based on Dysregulated Immune LncRNAs

Abstract

Long noncoding RNAs (lncRNAs) perform indispensable functions in cancer pathologies and are involved in the onset and progression of multiple cancers. Multiple platforms were performed to comprehensively analyze the head and neck squamous cell carcinoma (HNSCC) for determining molecular subtypes. Molecular subtypes were clustered and analyzed by the “ConsensusClusterPlus” R package. The Limma software was utilized to screen for differentially expressed genes (DEGs). Functional enrichment analyses, including Gene Set Enrichment Analysis (GSEA), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Ontology (GO), were performed on the three database resources. Seventeen lncRNAs were determined as HNSCC-specific immune lncRNAs that were dysregulated. Our research identified and redefined two distinct molecular subtypes, C1 (230 samples) and C2 (269 samples). Moreover, the C1 subtype had a higher survival rate than the C2 subtype in HNSCC samples, as well as a prolonged median survival duration with activated immune response. 1531 DEGs, including 529 upmodulated genes and 1002 downmodulated genes, were identified in the above two subtypes. Functional enrichment analysis revealed that upmodulated genes in C2 were associated with tumorigenesis and development, while downregulated genes in C2 were associated with immune response. By comparing with the existing immunophenotyping group, it found that C1 had more overlaps with the existing Atypical and Basal, and C2 and Classical and Mesenchymal had a high degree of coincidence. On the basis of lncRNA, there were significant differences in the aspect of prognostic and immunological characteristics in the two identified molecular subtypes of HNSCC.