Molecular Subtypes Based on Cell Differentiation Trajectories in Head and Neck Squamous Cell Carcinoma: Differential Prognosis and Immunotherapeutic Responses

Frontiers in Immunology

Lu-Lu Lin¹  Hui-Yun Gu²  Chao Hu²  Ren-Xiong Wei²  Zhen-Dong Huang³  Yan-Yi Liu³  Yong-Cheng Fu⁴  Zi-Zhen Liu⁴ 

[1] Department of Pathology and Pathophysiology, School of Basic Medicine, Wuhan University, Wuhan, China;Department of Spine and Orthopedic Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China;Department of Stomatology, Southern Medical University, Guangzhou, China;The Third Clinical School, Hubei University of Medicine, Shiyan, China;

关键词: head and neck squamous cell carcinoma;    cell differentiation trajectory;    single-cell sequencing;    molecular subtype;    immunotherapy response;   

DOI  :  10.3389/fimmu.2021.791621

来源: DOAJ

【 摘 要 】

ObjectiveHead 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.MethodsBased 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.ResultsHNSCCs 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.ConclusionsThis 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.

【 授权许可】

Unknown