Identification of genetic mechanisms underlying lipid metabolism-mediated tumor immunity in head and neck squamous cell carcinoma

Shaokun Liu; Shuning Wang; Zhenlin Wang

doi:10.1186/s12920-023-01543-6

Identification of genetic mechanisms underlying lipid metabolism-mediated tumor immunity in head and neck squamous cell carcinoma

BMC Med Genomics. 2023 May 20;16(1):110. doi: 10.1186/s12920-023-01543-6.

Authors

Shaokun Liu^#¹, Shuning Wang^#², Zhenlin Wang³

Affiliations

¹ Department of Otorhinolaryngology Head and Neck Surgery, Xuanwu Hospital Capital Medical University, No. 45 Changchun Street, Xicheng District, Beijing, 100053, China.
² Capital Medical University, No.10 Xitou Tiao, You'an Menwai, Fengtai District, Beijing, 10069, China.
³ Department of Otorhinolaryngology Head and Neck Surgery, Xuanwu Hospital Capital Medical University, No. 45 Changchun Street, Xicheng District, Beijing, 100053, China. wzl1812@xwhosp.org.

^# Contributed equally.

Abstract

Objective: To identify the genetic mechanisms underlying lipid metabolism-mediated tumor immunity in head and neck squamous carcinoma (HNSC).

Materials and methods: RNA sequencing data and clinical characteristics of HNSC patients were procured from The Cancer Genome Atlas (TCGA) database. Lipid metabolism-related genes were collected from KEGG and MSigDB databases. Immune cells and immune-related genes were obtained from the TISIDB database. The differentially expressed genes (DEGs) in HNSC were identified and weighted correlation network analysis (WGCNA) was performed to identify the significant gene modules. Lasso regression analysis was performed to identify hub genes. The differential gene expression pattern, diagnostic values, relationships with clinical features, prognostic values, relationships with tumor mutation burden (TMB), and signaling pathways involved, were each investigated.

Results: One thousand six hundred sixty-eight DEGs were identified as dysregulated between HNSC tumor samples and healthy control head and neck samples. WGCNA analysis and Lasso regression analysis identified 8 hub genes, including 3 immune-related genes (PLA2G2D, TNFAIP8L2 and CYP27A1) and 5 lipid metabolism-related genes (FOXP3, IL21R, ITGAL, TRAF1 and WIPF1). Except CYP27A1, the other hub genes were upregulated in HNSC as compared with healthy control samples, and a low expression of these hub genes indicated a higher risk of death in HNSC. Except PLA2G2D, all other hub genes were significantly and negatively related with TMB in HNSC. The hub genes were implicated in several immune-related signaling pathways including T cell receptor signaling, Th17 cell differentiation, and natural killer (NK) cell mediated cytotoxicity.

Conclusion: Three immune genes (PLA2G2D, TNFAIP8L2, and CYP27A1) and immune-related pathways (T cell receptor signaling, Th17 cell differentiation, and natural killer (NK) cell mediated cytotoxicity) were predicted to play significant roles in the lipid metabolism-mediated tumor immunity in HNSC.

Keywords: Bioinformatics; Head and neck squamous carcinoma; Lipid metabolism; Tumor immunity.

MeSH terms

Biomarkers, Tumor / genetics
Cytoskeletal Proteins / metabolism
Head and Neck Neoplasms* / genetics
Humans
Intracellular Signaling Peptides and Proteins
Lipid Metabolism* / genetics
Prognosis
Receptors, Antigen, T-Cell / metabolism
Squamous Cell Carcinoma of Head and Neck / genetics

Substances

Biomarkers, Tumor
Receptors, Antigen, T-Cell
WIPF1 protein, human
Cytoskeletal Proteins
Intracellular Signaling Peptides and Proteins