Abstract 69P
Background
Oral Squamous Cell Carcinoma (OSCC) remains a significant health burden globally, necessitating a comprehensive understanding of its underlying molecular mechanisms. Hypoxia, a hallmark of solid tumors, profoundly influences cancer progression, therapeutic response, and major cause of reoccurrence. This study aimed to elucidate the metabolic alterations associated with hypoxia-induced OSCC cell lines using a proteomics and metabolomics approach.
Methods
Human OSCC cell lines were cultured under normoxic and hypoxic conditions. Hypoxia induction was validated by western blot. Cell proliferation and migration were observed by MTT assay and scratch assay respectively. Subsequently, proteomics and metabolomics were employed. Bioinformatic tools were used to analyze the data, identifying key metabolic pathways affected by hypoxia in OSCC cells. Further, TCGA data was used for identify the enriched pathway in different Hypoxia enriched cluster through ssGSEA, GSEA, and differential analysis.
Results
Integrated analysis of the OMIC data revealed substantial alterations in arginine and proline metabolism in OSCC cells subjected to hypoxic conditions. The expression levels of key enzymes involved in these metabolic pathways, such as argininosuccinate synthase 1 (ASS1) were significantly dysregulated. Furthermore, downstream metabolites, including ornithine and polyamines; spermidine, and spermine exhibited significant changes under hypoxic stress. These alterations suggested a potential critical role of arginine and proline metabolism in OSCC adaptation to hypoxic stress. Further, TCGA data analysis reveals cell proliferative, migration, angiogenesis, and EMT pathways are enriched in high hypoxic score clusters. Clusters showing high hypoxia enrichment scores have a low survival rate.
Conclusions
This integrated OMIC analysis sheds light on the dysregulation of Arginine and proline metabolism and other cancer-specific pathways that may contribute to tumor adaptation and survival under low-oxygen conditions. Understanding the metabolic rewiring in hypoxia-driven OSCC could unveil new therapeutic targets and strategies for combating this aggressive malignancy.
Editorial acknowledgement
Clinical trial identification
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
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