Image_2_Molecular Subtypes Based on Cell Differentiation Trajectories in Head and Neck Squamous Cell Carcinoma: Differential Prognosis and Immunothera.tif (21.34 MB)
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Image_2_Molecular Subtypes Based on Cell Differentiation Trajectories in Head and Neck Squamous Cell Carcinoma: Differential Prognosis and Immunotherapeutic Responses.tif

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posted on 24.12.2021, 04:17 by Zhen-Dong Huang, Zi-Zhen Liu, Yan-Yi Liu, Yong-Cheng Fu, Lu-Lu Lin, Chao Hu, Hui-Yun Gu, Ren-Xiong Wei
Objective

Head and neck squamous cell carcinoma (HNSCC) is one of the most common and lethal malignant tumors. We aimed to investigate the HNSCC cell differentiation trajectories and the corresponding clinical relevance.

Methods

Based on HNSCC cell differentiation-related genes (HDRGs) identified by single-cell sequencing analysis, the molecular subtypes and corresponding immunity, metabolism, and stemness characteristics of 866 HNSCC cases were comprehensively analyzed. Machine-learning strategies were used to develop a HNSCC cell differentiation score (HCDscore) in order to quantify the unique heterogeneity of individual samples. We also assessed the prognostic value and biological characteristics of HCDscore using the multi-omics data.

Results

HNSCCs were stratified into three distinct molecular subtypes based on HDRGs: active stroma (Cluster-A), active metabolism (Cluster-B), and active immune (Cluster-C) types. The three molecular subtypes had different characteristics in terms of biological phenotype, genome and epigenetics, prognosis, immunotherapy and chemotherapy responses. We then demonstrated the correlations between HCDscore and the immune microenvironment, subtypes, carcinogenic biological processes, genetic variation, and prognosis. The low-HCDscore group was characterized by activation of immunity, enhanced response to anti-PD-1/PD-L1 immunotherapy, and better survival compared to the high-HCDscore group. Finally, by integrating the HCDscore with prognostic clinicopathological characteristics, a nomogram with strong predictive performance and high accuracy was constructed.

Conclusions

This study revealed that the cell differentiation trajectories in HNSCC played a nonnegligible role in patient prognosis, biological characteristics, and immune responses. Evaluating cancer cell differentiation will help to develop more effective immunotherapy, metabolic therapy, and chemotherapy strategies.

History

References