Circadian rhythm-related genes index: A predictor for HNSCC prognosis, immunotherapy efficacy, and chemosensitivity

Frontiers in Immunology

Immunology

Hao Chi¹  Gaoge Peng¹  Zhijia Xia²  Jinhui Liu³  Gang Tian⁴  Jinyan Yang⁵  Jinhao Zhang⁵  Xixi Xie⁵  Guobin Song⁵ 

[1] Clinical Medical College, Southwest Medical University, Luzhou, China;Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, Munich, Germany;Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China;Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, China;School of Stomatology, Southwest Medical University, Luzhou, China;

关键词: HNSCC;    circadian rhythm;    biomarkers;    tumor microenvironment;    immunotherapy;    prognostic signature;   

DOI  :  10.3389/fimmu.2023.1091218

 received in 2022-11-06, accepted in 2023-02-27,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundHead and neck squamous cell carcinoma (HNSCC) is the most common head and neck cancer and is highly aggressive and heterogeneous, leading to variable prognosis and immunotherapy outcomes. Circadian rhythm alterations in tumourigenesis are of equal importance to genetic factors and several biologic clock genes are considered to be prognostic biomarkers for various cancers. The aim of this study was to establish reliable markers based on biologic clock genes, thus providing a new perspective for assessing immunotherapy response and prognosis in patients with HNSCC.MethodsWe used 502 HNSCC samples and 44 normal samples from the TCGA-HNSCC dataset as the training set. 97 samples from GSE41613 were used as an external validation set. Prognostic characteristics of circadian rhythm-related genes (CRRGs) were established by Lasso, random forest and stepwise multifactorial Cox. Multivariate analysis revealed that CRRGs characteristics were independent predictors of HNSCC, with patients in the high-risk group having a worse prognosis than those in the low-risk group. The relevance of CRRGs to the immune microenvironment and immunotherapy was assessed by an integrated algorithm.Results6-CRRGs were considered to be strongly associated with HNSCC prognosis and a good predictor of HNSCC. The riskscore established by the 6-CRRG was found to be an independent prognostic factor for HNSCC in multifactorial analysis, with patients in the low-risk group having a higher overall survival (OS) than the high-risk group. Nomogram prediction maps constructed from clinical characteristics and riskscore had good prognostic power. Patients in the low-risk group had higher levels of immune infiltration and immune checkpoint expression and were more likely to benefit from immunotherapy.Conclusion6-CRRGs play a key predictive role for the prognosis of HNSCC patients and can guide physicians in selecting potential responders to prioritise immunotherapy, which could facilitate further research in precision immuno-oncology.

【 授权许可】

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Copyright © 2023 Chi, Yang, Peng, Zhang, Song, Xie, Xia, Liu and Tian