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Translational Therapeutics

Relationship between the expression of PD-L1 and 18F-FDG uptake in pancreatic ductal adenocarcinoma

British Journal of Cancer volume 129, pages 541–550 (2023)Cite this article

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Abstract

Background

PD-L1 promotes glycolysis in tumour cells. We observed a correlation between high PD-L1 expression and high 18F-FDG uptake in patients with pancreatic ductal adenocarcinoma (PDAC) in a previous study. This study aims to determine the usefulness of 18F-FDG PET/CT for evaluating the PD-L1 status in PDAC and to elucidate its rationality by integrated analyses.

Methods

For bioinformatics analysis, WGCNA, GSEA and TIMER were applied to analyse the pathways and hub genes associated with PD-L1 and glucose uptake. 18F-FDG uptake assay was used to determine the glucose uptake rate of PDAC cells in vitro. Related genes expression were verified by RT-PCR and western blot. A retrospective analysis was performed on 47 patients with PDAC who had undergone 18F-FDG PET/CT. Maximum standardised uptake values (SUVmax) were determined. The usefulness of SUVmax for evaluating PD-L1 status was determined by receiver operating characteristic (ROC) curve analysis.

Results

Bioinformatics analysis showed that several signalling pathways are associated with both PD-L1 expression and tumour glucose uptake, among which JAK-STAT may be an important one. By in vitro experiments, the regulatory role of PD-L1 on glucose uptake was demonstrated, and its dependency on the JAK-STAT pathway was also verified by the rescue study. The SUVmax of PD-L1-positive patients was significantly higher than PD-L1-negative in tumour cells (TCs) (6.1 ± 2.3 vs. 11.1 ± 4.2; P < 0.001), and in tumour-infiltrating immune cells (TIICs) (6.4 ± 3.2 vs. 8.4 ± 3.5; P < 0.001). In a multivariate analysis, SUVmax was significantly associated with PD-L1 expression in TCs and TIICs (P < 0.001 and P = 0.018, respectively). Using SUVmax cut-off values of 8.15 and 7.75, PD-L1 status in TCs and TIICs could be predicted with accuracies of 91.5% and 74.5%, respectively.

Conclusion

Higher 18F-FDG uptake by PDAC is associated with elevated PD-L1 expression. JAK-STAT is an important pathway that mediates PD-L1 to promote glucose uptake in PDAC.

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Fig. 1: Flowchart of this study.
Fig. 2: Weighted correlation network analysis (WGCNA).
Fig. 3: Gene Set Enrichment Analysis (GSEA) of the correlation between PD-L1 gene expression level and gene sets in Kyoto Gene and Genome Encyclopedia (KEGG) pathways.
Fig. 4: The regulation of PD-L1 on 18F-FDG uptake had a dependence on the JAK-STAT pathway.
Fig. 5: Representative images of the IHC and PET/CT.
Fig. 6: The association between 18F-FDG accumulation and PD-L1 status in TCs/TIICs of pancreatic ductal adenocarcinoma (n = 47).
Fig. 7: Mechanism diagram of this study.

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Data availability

All analysed and derivative raw data are available on request.

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Acknowledgements

We are grateful to the physicians, nurses, and all the patients who participated in this research.

Funding

The study was sponsored by the National Key Research and Development Program of China (2021YFA0910000 and 2020YFA0909000), the Interdisciplinary Program of Shanghai Jiao Tong University (ZH2018QNA41), and the National Natural Science Foundation of China (Nos. 81771858 and 82171972).

Author information

Author notes

  1. These authors contributed equally: Jiajin Li, Ruohua Chen, Yumei Chen.

Authors and Affiliations

  1. Department of Nuclear Medicine, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, 200127, Shanghai, China

    Jiajin Li, Ruohua Chen, Yumei Chen, Xiang Zhou, Qian Xia, Cheng wang, Liangrong Wan, Haiqin Bao, Gang Huang & Jianjun Liu

  2. Institute of Clinical Nuclear Medicine, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, 200127, Shanghai, China

    Jiajin Li, Ruohua Chen, Yumei Chen, Xiang Zhou, Cheng wang, Liangrong Wan, Haiqin Bao, Gang Huang & Jianjun Liu

  3. Department of Oncology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, 200127, Shanghai, China

    Qing Xia

  4. Institute of Molecular Medicine, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, 200127, Shanghai, China

    Qian Xia

  5. Shanghai Key Laboratory of Molecular Imaging, Shanghai University of Medicine and Health Sciences, 201318, Shanghai, China

    Gang Huang

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Contributions

All authors contributed to the study’s conception and design. Material preparation, data collection and analysis were performed by Jiajin Li, XiaQing, Cheng Wang, Liangrong Wan and Haiqin Bao. The first draft of the manuscript was written by Jiajin Li, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Gang Huang or Jianjun Liu.

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The authors declare no competing interests.

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All procedures performed in studies involving human participants were approved by the Institutional Review Board of Shanghai Jiao Tong University-affiliated Ren Ji Hospital and with the principles of the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. This article does not describe any studies with animals performed by any of the authors.

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Li, J., Chen, R., Chen, Y. et al. Relationship between the expression of PD-L1 and 18F-FDG uptake in pancreatic ductal adenocarcinoma. Br J Cancer 129, 541–550 (2023). https://doi.org/10.1038/s41416-023-02297-9

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