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
- 1 Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong University, Jinan, Shandong 250299, P.R. China
- 2 Radiotherapy Department, Shandong Second Provincial General Hospital, Shandong University, Jinan, Shandong 250299, P.R. China
- 3 Department of Gastrointestinal Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, P.R. China
- 4 Department 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
- 5 Department of Respiratory and Critical Care Medicine, Shandong Second Provincial General Hospital, Jinan, Shandong 250299, P.R. China
- 6 Department of Oncology, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250299, P.R. China
- 7 Generalsurgery Department, Wenshang County People’s Hospital, Wenshang, Shandong 272500, P.R. China
- 8 Department of Thoracic Surgery, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong 250117, P.R. China
- 9 Department of Hepatobiliary Intervention, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, P.R. China
- 10 Department of Gastrointestinal Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, Shandong 264000, P.R. China
- 11 Department of Cardiology, The Second Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250033, P.R. China
Received: June 5, 2023 Accepted: November 2, 2023 Published: December 28, 2023
https://doi.org/10.18632/aging.205323How to Cite
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.
Abbreviations
FPKM: fragments per kilobase of exon per million fragments mapped; FFPE: formalin fixation and paraffin embedding; IHC: immunohistochemical; OS: overall survival; HNSCC: head and neck squamous cell carcinoma; OSRS: oxidative stress-related gene scoring model; TCGA: The Cancer Genome Atlas; GEO: Gene Expression Omnibus; GSE: GEO Series; TME: tumor microenvironment; ECM: extracellular matrix; TAM: tumor-associated macrophages; MDSCs: myeloid-derived suppressor cells; CTLs: cytotoxic T lymphocytes; ROS: reactive oxygen species; NK: natural killer; DEGs: differentially expressed genes; HR: hazard ratio; LASSO: least absolute shrinkage and selection operator; GSVA: gene set variation analysis; KEGG: Kyoto Encyclopedia of Genes and Genomes; GDSC: Genomics of Drug Sensitivity in Cancer; CTRP: Cancer Therapeutics Response Portal; TF: transcription factors; CSI: Connection Specificity Index; ICIs: immune checkpoint inhibitors; UMAP: Uniform Manifold Approximation and Projection; OSPS: oxidative stress prognostic signature; RSS: Regulon Specificity Score.