China Oncology ›› 2020, Vol. 30 ›› Issue (4): 261-267.doi: 10.19401/j.cnki.1007-3639.2020.04.004

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The mechanism of protein tyrosine phosphatase receptor type delta affecting expression of PD-L1 in hepatocellular carcinoma via STAT3 pathway

MENG Qiuhua, TIAN Jing, QIN Yan, MENG Qiuxiao, DONG Min   

  1. School of Pharmacy, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
  • Online:2020-04-30 Published:2020-05-11
  • Contact: DONG Min E-mail: dongmin0217@sina.com

Abstract: Background and purpose: The aberrant expressions of protein tyrosine phosphatase receptor type delta (PTPRD) and programmed death ligand 1 (PD-L1) in hepatocellular carcinoma are related to tumor invasion and metastasis. It is well recognized that signal transducer and activator of transcription-3 (STAT3) plays a critical role in cancer. It also affects many aspects of the immune system. Aberrant activation of STAT3 is closely related to the abnormal expressions of PTPRD and PD-L1. However, until now, few reports demonstrated the correlation between PTPRD and PD-L1. This study aimed to investigate the expressions and correlation of PTPRD and PD-L1 and whether PTPRD regulates PD-L1 in hepatocellular carcinoma tissues, and draw out the underlying mechanisms in this process. Methods: Expression levels of PD-L1 and PTPRD in hepatocellular carcinoma tissues from 16 patients with hepatocellular carcinoma receiving surgery in Guangxi Medical University during Oct. 2018 to Jan. 2019 were detected by immunochemistry and real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR), and their relationship was analyzed. The effects of overexpression or knockdown of PTPRD on PD-L1, STAT3 and p-STAT3 protein expressions were detected by Western blot, and PD-L1 mRNA expression was detected by RTFQ-PCR. Results: The expression of PTPRD was significantly lower in hepatocellular carcinoma tissues than in adjacent tissues (P<0.05), while the expression of PD-L1 was significantly higher (P<0.05).There was a negative correlation between PTPRD and PD-L1 expressions in hepatocellular carcinoma (r 2 =0.275 8, P=0.036 7). The protein expressions of PD-L1, STAT3 and p-STAT3 were down-regulated when PTPRD was overexpressed (P<0.05), while the expression level of PD-L1was increased in tissues with PTPRD knockdown (P<0.05). Conclusion: PTPRD and PD-L1 are negatively correlated in hepatocellular carcinoma. PTPRD regulates PD-L1 expression through the STAT3 pathway, and it is expected to become a new target for the immunotherapy of hepatocellular carcinoma.

Key words: Protein tyrosine phosphatase receptor type delta, Programmed death ligand-1, Signal transducer and activator of transcription pathway, Hepatocellular carcinoma