AUTHOR=Chen Fang , Gong Xin , Xia Meng , Yu Feng , Wu Jian , Yu Chaosheng , Li Junzheng 

TITLE=The Aging-Related Prognostic Signature Reveals the Landscape of the Tumor Immune Microenvironment in Head and Neck Squamous Cell Carcinoma

JOURNAL=Frontiers in Oncology

VOLUME=Volume 12 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.857994

DOI=10.3389/fonc.2022.857994

ISSN=2234-943X

ABSTRACT=Background: Numerous studies have shown that the aging microenvironment played a huge impact on tumor progression. However, the clinical prognostic value of aging-related risk signatures and their effects on tumor immune microenvironment (TIME) in head and neck squamous cell carcinoma (HNSCC) remains largely unclear. This study aimed to identify novel prognostic signature based on aging-related genes (AGs) and reveal the landscape of TIME in HNSCC. Methods: Differentially expressed AGs were identified using the gene set enrichment analysis (GESA). The prognostic risk model of AGs was established by Univariate and multivariate Cox regression and LASSO regression analyses. The independent prognostic value of the risk model and the correlations of the prognostic signature with immune score, tumor immune cells infiltration and immune checkpoints were systematically analyzed. Results: A prognostic risk model of four AGs (BAK1, DKK1, CDKN2A and MIF) was constructed and validated in the training and testing datasets. Kaplan-Meier curves and time-dependent ROC analysis confirmed that the four-AG risk signature possessed accurate predictive value for prognosis in patients with HNSCC. Correlation analysis revealed that the risk score was negatively associated with immune score and immune cell infiltration level while positively correlated with immune checkpoint blockade (ICB) response score. Patients of the high-risk subtype contained higher infiltration levels of resting NK cells, M0 macrophages, M2 macrophages, and resting mast cells while lower infiltration levels of memory B cells, CD8+ T cells, follicular helper T cells, regulatory T cells (Tregs), activated mast cells than did those of the low-risk subtype. The expressions of CTLA4, PDCD1, and TIGIT were down-regulated while PDCD1LG2 expression was up-regulated in the high-risk subtype compared to that in the low-risk subtype. Furthermore, the four selected AGs in risk model were demonstrated to possess important functions in immune cell infiltration and ICB response of HNSCC. Conclusions: The aging-related risk signature is a reliable prognostic model for predicting survival of HNSCC patients and provides potential targets for improving outcomes of immunotherapy.