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Research Paper|Volume 15, Issue 24|pp 14957—14984

A novel oxidative stress-related gene signature as an indicator of prognosis and immunotherapy responses in HNSCC

Zhuoqi Li1,2, Chunning Zheng3, Hongtao Liu4, Jiling Lv5, Yuanyuan Wang6, Kai Zhang7, Shuai Kong3, Feng Chen8, Yongmei Kong1,2, Xiaowei Yang9, Yuxia Cheng4, Zhensong Yang10, Chi Zhang11, Yuan Tian1,2
  • 1Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong University, Jinan, Shandong 250299, P.R. China
  • 2Radiotherapy Department, Shandong Second Provincial General Hospital, Shandong University, Jinan, Shandong 250299, P.R. China
  • 3Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, P.R. China
  • 4Department of Pathology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Medicine and Health Key Laboratory of Clinical Pathology, Shandong Lung Cancer Institute, Shandong Institute of Nephrology, Jinan, Shandong 250014, P.R. China
  • 5Department of Respiratory and Critical Care Medicine, Shandong Second Provincial General Hospital, Jinan, Shandong 250299, P.R. China
  • 6Department of Oncology, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250299, P.R. China
  • 7Generalsurgery Department, Wenshang County People’s Hospital, Wenshang, Shandong 272500, P.R. China
  • 8Department of Thoracic Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250117, P.R. China
  • 9Department of Hepatobiliary Intervention, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, P.R. China
  • 10Department of Gastrointestinal Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong 264000, P.R. China
  • 11Department of Cardiology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250033, P.R. China
* Equal contribution
Received: June 5, 2023Accepted: November 2, 2023Published: December 28, 2023
https://doi.org/10.18632/aging.205323

Copyright: © 2023 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Purpose: To identify molecular subtypes of oxidative stress-related genes in head and neck squamous cell carcinoma (HNSCC) and to construct a scoring model of oxidative stress-related genes.

Methods: R language based scRNA-seq and bulk RNA-seq analyses were used to identify molecular isoforms of oxidative stress-related genes in HNSCC. An oxidative stress-related gene scoring (OSRS) model was constructed, which were verified through online data and immunohistochemical staining of clinical samples.

Results: Using TCGA-HNSCC datasets, nine predictive genes for overall patient survival, rarely reported in previous similar studies, were screened. AREG and CES1 were identified as prognostic risk factors. CSTA, FDCSP, JCHAIN, IFFO2, PGLYRP4, SPOCK2 and SPINK6 were identified as prognostic factors. Collectively, all genes formed a prognostic risk signature model for oxidative stress in HNSCC, which were validated in GSE41613, GSE103322 and PRJEB23709 datasets. Immunohistochemical staining of SPINK6 in nasopharyngeal cancer samples validated the gene panel. Subsequent analysis indicated that subgroups of the oxidative stress prognostic signature played important roles during cellular communication, the immune microenvironment, the differential activation of transcription factors, oxidative stress and immunotherapeutic responses.

Conclusions: The risk model might predict HNSCC prognosis and immunotherapeutic responses.