Identification of a gene score related to antigen processing and presentation machinery for predicting prognosis in head and neck squamous cell carcinoma and its potential implications for immunotherapy.
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引用次数: 0
Abstract
Background: Despite its crucial role in immune surveillance and cell survival of tumors, the significance of MHC antigen processing and presentation machinery (APM) is still not fully understood in head and neck squamous cell carcinoma (HNSCC). We sought to develop an APM gene score (APMGS) to predict prognosis and reveal the molecular and immune traits of the APMGS-defined subgroups in HNSCC.
Methods: Based on the APM-related genes acquired from 6 databases, 117 combined machine learning algorithms were applied to develop APMGS with The Cancer Genome Atlas (TCGA)-HNSCC database and validated with the Gene Expression Omnibus (GEO) dataset. Comprehensive analysis was performed to investigate the molecular and immune features of APMGS subgroups.
Results: The APMGS constructed by StepCox [both] + Ridge method achieved the highest C-index and area under curve (AUC) at 3 years and were thus adopted as the final model. Low-APMGS patients exhibited superior overall survival compared with high-APMGS patients in both TCGA and GEO cohorts. Subsequent analysis confirmed that a low APMGS was associated with immune response-related pathways; low TP53 mutation rate and low tumor mutation burden (TMB); a less aggressive phenotype; high infiltration of activated CD4+ memory T cells, CD8+ T cells, follicular helper T cells, and Tregs; active immunity; and higher sensitivity to chemotherapeutic and targeted agents. In contrast, a high APMGS linked to proteasome and protein export pathways; high TP53 mutation rate and high TMB; a more aggressive phenotype; high infiltration of M0 macrophages and eosinophils; suppressed immunity; and lower sensitivity to chemotherapeutic and targeted agents.
Conclusions: Our findings suggest that APMGS has potential to predict the prognosis, and molecular and immune characteristics of HNSCC, and may also serve as an indicator for immunotherapy benefit.
期刊介绍：
Clinical and Translational Oncology is an international journal devoted to fostering interaction between experimental and clinical oncology. It covers all aspects of research on cancer, from the more basic discoveries dealing with both cell and molecular biology of tumour cells, to the most advanced clinical assays of conventional and new drugs. In addition, the journal has a strong commitment to facilitating the transfer of knowledge from the basic laboratory to the clinical practice, with the publication of educational series devoted to closing the gap between molecular and clinical oncologists. Molecular biology of tumours, identification of new targets for cancer therapy, and new technologies for research and treatment of cancer are the major themes covered by the educational series. Full research articles on a broad spectrum of subjects, including the molecular and cellular bases of disease, aetiology, pathophysiology, pathology, epidemiology, clinical features, and the diagnosis, prognosis and treatment of cancer, will be considered for publication.
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