Characterization of Molecular Subtypes in Head and Neck Squamous Cell Carcinoma With Distinct Prognosis and Treatment Responsiveness

Abstract

Head and neck squamous cell carcinoma (HNSCC) is one of the most aggressive malignancies with complex phenotypic, etiological, biological, and clinical heterogeneities. Previous studies have proposed different clinically relevant subtypes of HNSCC, but little is known about its corresponding prognosis or suitable treatment strategy. Here, we identified 101 core genes from three prognostic pathways, including mTORC1 signaling, unfold protein response, and UV response UP, in 124 pairs of tumor and matched normal tissues of HNSCC. Moreover, we identified three robust subtypes associated with distinct molecular characteristics and clinical outcomes using consensus clustering based on the gene expression profiles of 944 HNSCC patients from four independent datasets. We then integrated the genomic information of The Cancer Genome Atlas (TCGA) HNSCC cohort to comprehensively evaluate the molecular features of different subtypes and screen for potentially effective therapeutic agents. Cluster 1 had more arrested oncogenic signaling, the highest immune cell infiltration, the highest immunotherapy and chemotherapeutic responsiveness, and the best prognosis. By contrast, Cluster 3 showed more activated oncogenic signaling, the lowest immune cell infiltration, the lowest immunotherapy and chemotherapy responsiveness, and the worst prognosis. Our findings corroborate the molecular diversity of HNSCC tumors and provide a novel classification strategy that may guide for prognosis and treatment allocation.

Identification of molecular classification and gene signature for predicting prognosis and immunotherapy response in HNSCC using cell differentiation trajectories

“…Sen et al recognized 2 prognostic and clinical immune subtypes of HNSCC, which differed in various aspects of prognosis, clinical outcomes, immune features, mutation pattern, biological functions, and response to immune checkpoint blockade therapy 22 . Zhang et al characterized 3 HNSCC subtypes with different molecular profiles and survival outcomes and proposed therapeutic drugs that might be suitable for specific subtypes 23 . Therefore, the exploration of individualized treatment modalities for HNSCC based on molecular subtypes is worthwhile.…”

“…Finally, we established a baseline for the examination of intra-tumoral heterogeneity and the detection of distinct molecular phenotypes in HNSCC using WGCNA, GO, and KEGG enrichment analysis. profiles and survival outcomes and proposed therapeutic drugs that might be suitable for specific subtypes 23 . Therefore, the exploration of individualized treatment modalities for HNSCC based on molecular subtypes is worthwhile.…”

Identification of a novel lipid metabolism-related gene signature for predicting colorectal cancer survival

“…Here, the consensus molecular subtypes were established using “ConsensusClusterPlus” package in R software ( Wilkerson and Hayes, 2010 ). In head and neck squamous cell carcinoma, the molecular features of different subtypes were evaluated for potentially effective therapeutic agents ( Zhang et al, 2021 ). In gastric cancer, consensus molecular subtypes were associated with immune infiltration for prediction of survival ( Yu et al, 2021a ).…”

Zinc Finger Proteins in Head and Neck Squamous Cell Carcinomas: ZNF540 May Serve as a Biomarker

“…For further explanation of whether these ZNFs were associated with more aggressive forms of HNSCC, we analyzed their expression profile in different molecular subtypes. We observed that all examined ZNFs were upregulated in the mesenchymal and less aggressive, atypical [ 30 ] tumors.…”