Abstract
Background
Mesothelioma (MESO) is an insidious malignancy with a complex diagnosis and a poor prognosis. Our study unveils Glutamine-Fructose-6-Phosphate Transaminase 2 (GFPT2) as a valuable diagnostic and prognostic marker for MESO, exploring its role in MESO pathogenesis.
Methods
We utilised tissue samples and clinicopathologic data to evaluate the diagnostic and prognostic significance of GFPT2 as a biomarker for MESO. The role of GFPT2 in the malignant progression of MESO was investigated through in vitro and in vivo experiments. The activation of NF-κB-p65 through O-GlcNAcylation at Ser75 was elucidated using experiments like HPLC-QTRAP-MS/MS and mass spectrometry analysis.
Results
The study demonstrates that GFPT2 exhibits a sensitivity of 92.60% in diagnosing MESO. Overexpression of it has been linked to an unfavourable prognosis. Through rigorous verification, we have confirmed that elevated GFPT2 levels drive malignant proliferation, invasiveness, and metastasis in MESO. At the molecular level, GFPT2 augments p65 O-GlcNAcylation, orchestrating its nuclear translocation and activating the NF-κB signalling pathway.
Conclusions
Our insights suggest GFPT2’s potential as a distinctive biomarker for MESO diagnosis and prognosis, and as an innovative therapeutic target, offering a new horizon for identification and treatment strategies in MESO management.
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Data availability
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.
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Funding
This work was supported by the Postgraduate Research & Practice Innovation Programme of Jiangsu Province (SJCX23_0708), and Nanjing Medical University.
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QG, JL, and FZ designed the experiments. JW, SZ, and GC performed the experiments. JW and SZ performed the data analyses. JW and SZ wrote the manuscript. TC, YW and JZ provided technical support and sample tissues. QG, JL, and FZ organised and supervised the study. All authors read and approved the final manuscript.
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The study was approved by The Ethics Committee of the First Affiliated Hospital of Nanjing Medical University (2023-SR-502). All animal care and experimental procedures were conducted according to the National Research Council’s Guidelines for the Care and Use of Laboratory Animals and were approved by the Institutional Animal Care and Use Committee (IACUC) of Nanjing Medical University (IACUC-2308001).
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Wei, J., Zhou, S., Chen, G. et al. GFPT2: A novel biomarker in mesothelioma for diagnosis and prognosis and its molecular mechanism in malignant progression. Br J Cancer (2024). https://doi.org/10.1038/s41416-024-02830-4
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DOI: https://doi.org/10.1038/s41416-024-02830-4