Abstract
Purpose
Oral squamous cell carcinomas (OSCCs) are primary head and neck malignant tumours with a high incidence and mortality. However, the molecular mechanisms involved in OSCC tumorigenesis are not fully understood.
Methods
OSCC and paired para-carcinoma samples were collected and used to perform multi-omics study. Transcriptomic analysis was used to reveal significant alterations in inflammatory and immune processes in OSCC. Ingenuity Pathway Analysis (IPA) combined with the LASSO Cox algorithm was used to identify and optimize a crucial gene signature. Metabolomics analysis was performed to identify the important metabolites which linked to the crucial gene signature. The public data TCGA-HNSCC cohort was used to perform the multiple bioinformatic analysis.
Results
These findings identified a FN1-mediated crucial network that was composed of immune-relevant genes (FN1, ACP5, CCL5, COL1A1, THBS1, BCAT1, PLAU, IGF2BP3, TNF, CSF2, CXCL1 and CXCL5) associated with immune infiltration and influences the tumour microenvironment, which may contribute to OSCC tumorigenesis and progression. Moreover, we integrated the relevant genes with altered metabolites identified by metabolic profiling and identified 7 crucial metabolites (Glu-Glu-Lys, Ser-Ala, Ser-Ala, N-(octadecanoyl) sphing-4-enine-1-phosphocholine, N-methylnicotinamide, pyrrhoxanthinol and xanthine) as potential downstream targets of the FN1-associated gene signature in OSCC. Importantly, FN1 expression is positively correlated with immune infiltration levels in HNSCC, which was confirmed at the single-cell level.
Conclusions
Overall, these results revealed the differential genetic and metabolic patterns associated with OSCC tumorigenesis and identified an essential molecular network that plays an oncogenic role in OSCC by affecting amino acid and purine metabolism. These genes and metabolites might, therefore, serve as predictive biomarkers of survival outcomes and potential targets for therapeutic intervention in OSCC.
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Availability of data and materials
The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: https://www.ncbi.nlm.nih.gov/, PRJNA876085 for transcriptomics raw data.
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Funding
This work was supported by the project from Hainan Province Clinical Medical Center, the Natural Science Fund of Hunan Province of China (grant number 2022JJ30846, 2021JJ30978, 2020JJ580, the National Natural Science Foundation of China (grant numbers 81802716).
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TFF: conceptualization; YCP: data curation, formal analysis, methodology, validation, visualization, and writing—original draft; DHY and XXL: data curation, formal analysis, methodology, validation, and visualization; KW, WL, YXH, XYL, ZHR, and XY: data curation and investigation; TFF, ZYZ, and SZ: formal analysis, funding acquisition, project administration, supervision, validation, visualization, writing—review and editing. All authors have read and approved the final version of this manuscript.
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OSCC and paired para-carcinoma samples were collected from the Department of Oral and Maxillofacial Surgery, the Second Xiangya Hospital of Central South University. Informed consent was obtained from all participants in writing. The protocols were approved by the Clinical Research Ethics Committee of the Second Xiangya Hospital of Central South University (NO. JBWKQA001), and the provisions of the Helsinki Declaration were followed when conducting the research.
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Peng, Y., Yin, D., Li, X. et al. Integration of transcriptomics and metabolomics reveals a novel gene signature guided by FN1 associated with immune response in oral squamous cell carcinoma tumorigenesis. J Cancer Res Clin Oncol 149, 6097–6113 (2023). https://doi.org/10.1007/s00432-023-04572-x
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DOI: https://doi.org/10.1007/s00432-023-04572-x