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Molecular Diagnostics

GFPT2: A novel biomarker in mesothelioma for diagnosis and prognosis and its molecular mechanism in malignant progression

British Journal of Cancer (2024)Cite this article

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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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Fig. 1: Identification of GFPT2 overexpression in MESO.
Fig. 2: Assessment of the utility of GFPT2 in the diagnosis and prognosis of MESO.
Fig. 3: Impact of GFPT2 on MESO cells proliferation, migration, and invasion.
Fig. 4: GFPT2 promotes the tumour growth and metastasis of MESO in vivo.
Fig. 5: NF-κB-p65 is involved in the GFPT2-induced MESO progression.
Fig. 6: GFPT2 facilitates p65 nuclear translocation via O-GlcNAcylation augmentation.

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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.

Author information

Author notes

  1. These authors contributed equally: Jia Wei, Suiqing Zhou, Gang Chen.

Authors and Affiliations

  1. Department of Pathology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China

    Jia Wei, Gang Chen & Qixing Gong

  2. Hepatobiliary Center, The First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, NHC Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, China

    Suiqing Zhou

  3. Department of Pathology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu Province, China

    Tingting Chen

  4. Department of Pathology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China

    Yan Wang

  5. Department of Pathology, Nanjing Chest Hospital, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China

    Jue Zou

  6. Jiangsu Provincial Key Laboratory of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, Jiangsu, China

    Fang Zhou & Jiali Liu

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  1. Jia Wei
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Contributions

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.

Corresponding authors

Correspondence to Fang Zhou, Jiali Liu or Qixing Gong.

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The authors declare no conficts of interest.

Ethics approval and consent to participate

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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