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Background <p>Oral squamous cell carcinogenesis is a complex biological process, although some progress has been made in predicting the risk of malignant transformation of oral squamous cell carcinoma (OSCC). We aimed to visualise the dynamic metabolic characteristics of the progression of OSCC using desorption electrospray ionisation mass spectrometry imaging (DESI-MSI).</p> Methods <p>Eight matched OSCC samples were analysed using DESI-MSI. MetaboAnalyst database was used to screen for differential metabolism, and perform metabolic pathway analysis. Key pathways and enzymes were validated using immunohistochemical (IHC) techniques in an additional 60 patients with OSCC. Knockdown OSCC cell lines were constructed and functional experiments were carried out to elucidate the effect of key enzyme on the proliferation and migration of OSCC.</p> Results <p>Spatial metabolomics revealed 55 differential metabolites between cancer and normal mucosal tissues, 59 between cancer and precancerous tissues, and 52 between precancerous and normal mucosal tissues. We further identified 30 metabolites that were either increased or decreased from normal tissues to precancerous lesions and then to cancer tissues. Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway analysis confirmed that sphingolipid metabolism and biosynthesis of unsaturated fatty acids are the main metabolic pathways involved in OSCC. Dihydroceramide desaturase (DEGS1) is the key enzyme in sphingolipid metabolism and is involved in ceramide synthesis, which is closely related to tumour carcinogenesis. We further confirmed that high expression of DEGS1 predicts poor overall survival and disease-free survival, and is closely related to the pathological grade of the tumour. In multivariate COX regression analysis, high expression of DEGS1 in tumor cells was an independent risk factor for OS in OSCC patients. Moreover, we demonstrated that DEGS1 knockdown inhibited the proliferation and migration of OSCC cells in vitro.</p> Conclusion <p>Our study used DESI-MSI to uncover the progression of OSCC at the spatial metabolomics level, and discovered key metabolic molecules involved in the carcinogenesis of OSCC. Sphingolipid metabolism plays an important role in OSCC carcinogenesis, and its key metabolic enzyme, DEGS1, is expected to become a new therapeutic target for OSCC in the future.</p>

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Spatial metabolomics atlas in the progression of oral squamous cell carcinoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月29日

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  • Huiting Zhao,
  • Wei Han,
  • Chaowen Shi,
  • Guanfa Luo,
  • Wen Lu,
  • Yujuan Fu,
  • Qingang Hu,
  • Xiaowei Song,
  • Zhengjun Shang,
  • Xihu Yang

摘要

Background

Oral squamous cell carcinogenesis is a complex biological process, although some progress has been made in predicting the risk of malignant transformation of oral squamous cell carcinoma (OSCC). We aimed to visualise the dynamic metabolic characteristics of the progression of OSCC using desorption electrospray ionisation mass spectrometry imaging (DESI-MSI).

Methods

Eight matched OSCC samples were analysed using DESI-MSI. MetaboAnalyst database was used to screen for differential metabolism, and perform metabolic pathway analysis. Key pathways and enzymes were validated using immunohistochemical (IHC) techniques in an additional 60 patients with OSCC. Knockdown OSCC cell lines were constructed and functional experiments were carried out to elucidate the effect of key enzyme on the proliferation and migration of OSCC.

Results

Spatial metabolomics revealed 55 differential metabolites between cancer and normal mucosal tissues, 59 between cancer and precancerous tissues, and 52 between precancerous and normal mucosal tissues. We further identified 30 metabolites that were either increased or decreased from normal tissues to precancerous lesions and then to cancer tissues. Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway analysis confirmed that sphingolipid metabolism and biosynthesis of unsaturated fatty acids are the main metabolic pathways involved in OSCC. Dihydroceramide desaturase (DEGS1) is the key enzyme in sphingolipid metabolism and is involved in ceramide synthesis, which is closely related to tumour carcinogenesis. We further confirmed that high expression of DEGS1 predicts poor overall survival and disease-free survival, and is closely related to the pathological grade of the tumour. In multivariate COX regression analysis, high expression of DEGS1 in tumor cells was an independent risk factor for OS in OSCC patients. Moreover, we demonstrated that DEGS1 knockdown inhibited the proliferation and migration of OSCC cells in vitro.

Conclusion

Our study used DESI-MSI to uncover the progression of OSCC at the spatial metabolomics level, and discovered key metabolic molecules involved in the carcinogenesis of OSCC. Sphingolipid metabolism plays an important role in OSCC carcinogenesis, and its key metabolic enzyme, DEGS1, is expected to become a new therapeutic target for OSCC in the future.