Increased ¹⁸F-FDGuptake on PET in hepatocellular carcinoma is associated with level ofPDL1 expression that regulated by beta-catenin

Objectives: Recently, the use of monoclonal antibodies to block immunosuppressive molecules in malignant tumors to improve the immune response to tumors has shown clinical therapeutic potential in advanced solid tumors. In this process, PDL1 plays an important role and is mainly expressed in malignant cancer. The glycolytic phenotype is a typical metabolic phenomenon that is prominent in cancer, as reflected by an increase in ¹⁸F-FDG uptake in PET / CT. Therefore, the anticancer effect of anti-PDL1 immunotherapy is predicted by studying the correlation between the expression level of PDL1 and FDG PET / CT in hepatocellular carcinoma.

Methods: Using PET / CT, Hepatocellular carcinomas were classified into High ¹⁸F-FDG/ low ¹¹C-acetate uptake HCCs and low ¹⁸F-FDG/ high ¹¹C-acetate uptake HCCs. The expression levels of PDL1, HIF1a and beta catenin were determined using immunohistochemistry (IHC) and western blotting analysis (WB) in the patient tissues of each group. Beta catenin expression was inhibited by siRNA against β-catenin and the regulation of PDL1 expression was confirmed in hepatocellular carcinoma cell lines.

Results: Glut1 expression was confirmed in order to confirm the sequential relationship between FDG PET / CT and Glut1 reflecting high glycolytic phenomena in HCC. Hepatocellular carcinomas with high ¹⁸F-FDG / low ¹¹C-acetate were highly expressed in cell membrane form. To investigate the correlation between PET/CT and PDL1 expression, IHC and WB were performed. The expression level of PDL1 was significantly higher in the HCC with high ¹⁸F-FDG / low ¹¹C-acetate uptake than HCC with low ¹⁸F-FDG / high ¹¹C-acetate HCC. PDL1 was also found to be highly expressed as membrane form, which has immunosuppressive function, and cytosolic part. The expression patterns of HIF-1α and β-catenin, which are related to malignant transformation of cancer, were confirmed to be highly expressed in cancer tissues. In particular, HCC with high ¹⁸F-FDG / low ¹¹C-acetate uptake was found to be highly expressed in nuclei capable of regulating gene expression. In order to confirm the association and controllability of the expression of PDL1 with catenin when β-catenin was inhibited by siRNA for β-catenin, expression of PDL1 was inhibited

Conclusion: The above results demonstrate that ¹⁸F-FDG PET/CT is closely related to the expression of PDL1 in HCC, and it is an important criterion that not only predicts the anti-cancer response of anti-PDL1 immunotherapy through that ¹⁸F-FDG PET/CT but also reflects the prognosis Research Support: This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP) (No. NRF-2011-0030086) and and was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (NRF-2016R1E1A1A01943303) and h was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT, and Future Planning (2012R1A1A3008042)