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

Hao Chi; Jinyan Yang; Gaoge Peng; Jinhao Zhang; Guobin Song; Xixi Xie; Zhijia Xia; Jinhui Liu; Gang Tian

doi:10.3389/fimmu.2023.1091218

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

Front Immunol. 2023 Mar 10:14:1091218. doi: 10.3389/fimmu.2023.1091218. eCollection 2023.

Authors

Hao Chi¹, Jinyan Yang², Gaoge Peng¹, Jinhao Zhang², Guobin Song², Xixi Xie², Zhijia Xia³, Jinhui Liu⁴, Gang Tian⁵

Affiliations

¹ Clinical Medical College, Southwest Medical University, Luzhou, China.
² School of Stomatology, Southwest Medical University, Luzhou, China.
³ Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, Munich, Germany.
⁴ Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
⁵ Department of Laboratory Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, China.

Abstract

Background: Head 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.

Methods: We 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.

Results: 6-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.

Conclusion: 6-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.

Keywords: HNSCC; biomarkers; circadian rhythm; immunotherapy; prognostic signature; tumor microenvironment.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Circadian Rhythm* / genetics
Head and Neck Neoplasms* / genetics
Head and Neck Neoplasms* / therapy
Humans
Immunotherapy
Prognosis
Squamous Cell Carcinoma of Head and Neck / genetics
Squamous Cell Carcinoma of Head and Neck / therapy
Tumor Microenvironment

Grants and funding

This study was supported by grants from the Luzhou Science and Technology Department Applied Basic Research Program (No: 2022-JYJ-145), and the Sichuan Province Science and Technology Department of foreign (border) high-end talent introduction project (No: 2023JDGD0037).