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

Frontiers in Cell and Developmental Biology

Faming Zhao¹  Fengzhen Cui¹  Xia Sheng²  Pei Zhang³  Shue Li⁵  Ji-Hua Shi⁶  Tingting Zhang⁶ 

[1] Ministry of Environmental Protection, State Key Laboratory of Environmental Health (Incubation), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;Department of Hepatobiliary and Pancreatic Surgery, Henan Key Laboratory of Digestive Organ Transplantation, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China;Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China;Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;Hubei Province Key Laboratory of Oral and Maxillofacial Development and Regeneration, Wuhan, China;;Key Laboratory of Environment and Health, Ministry of Education &

关键词: head and neck squamous cell carcinoma;    molecular subgroups;    gene expression;    tumor immune microenvironment;    prognosis;   

DOI  :  10.3389/fcell.2021.711348

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown