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

蒙秋华; 田　婧; 覃　妍; 蒙秋晓; 董　敏

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

更新时间：2026-01-27

- The mechanism of protein tyrosine phosphatase receptor type delta affecting expression of PD-L1 in hepatocellular carcinoma via STAT3 pathway
- China Oncology Vol. 30, Issue 4, Pages: 261-267(2020)
- 作者机构：
  
  广西医科大学药学院,广西,南宁,530021
- 作者简介：
- 基金信息：
- DOI：10.19401/j.cnki.1007-3639.2020.04.004
  CLC： R735.7
- Published Online：11 May 2020，
  
  Published：11 May 2020
- 稿件说明：
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蒙秋华, 田　婧, 覃　妍, 蒙秋晓, 董　敏. 蛋白酪氨酸磷酸酶受体D通过STAT3途径影响肝癌细胞PD-L1表达的机制研究[J]. 中国癌症杂志, 2020, 30(4): 261-267.

蒙秋华, 田　婧, 覃　妍, et al. The mechanism of protein tyrosine phosphatase receptor type delta affecting expression of PD-L1 in hepatocellular carcinoma via STAT3 pathway[J]. China Oncology, 2020, 30(4): 261-267.
蒙秋华, 田　婧, 覃　妍, 蒙秋晓, 董　敏. 蛋白酪氨酸磷酸酶受体D通过STAT3途径影响肝癌细胞PD-L1表达的机制研究[J]. 中国癌症杂志, 2020, 30(4): 261-267. DOI： 10.19401/j.cnki.1007-3639.2020.04.004.

蒙秋华, 田　婧, 覃　妍, et al. The mechanism of protein tyrosine phosphatase receptor type delta affecting expression of PD-L1 in hepatocellular carcinoma via STAT3 pathway[J]. China Oncology, 2020, 30(4): 261-267. DOI： 10.19401/j.cnki.1007-3639.2020.04.004.

摘要

背景与目的：蛋白酪氨酸磷酸酶受体D（protein tyrosine phosphatase receptor type delta，PTPRD）和程序性死亡［蛋白］配体-1（programmed death ligand-1，PD-L1）在肝癌组织的异常表达与肿瘤侵袭和转移有关。信号转导与转录激活因子3（signal transducer and activator of transcription-3，STAT3）通路在癌症中起着关键作用，影响免疫系统的许多方面，STAT3异常激活与PTPRD和PD-L1的异常表达密切相关，然而PTPRD和PD-L1的相关性目前鲜见文献报道。探讨PTPRD和PD-L1在肝癌组织中的表达相关性，进一步在肝癌细胞中观察PTPRD是否可调控PD-L1。方法：采用免疫组织化学法分析2018年10月—2019年1月广西医科大学附属肿瘤医院肝二病区收治的原发性肝癌并经手术治疗的16例肝癌患者的肿瘤标本及其癌旁标本中PTPRD和PD-L的蛋白水平，采用实时荧光定量聚合酶链反应（real-time fluorescence quantitative polymerase chain reaction，RTFQ-PCR）检测同一标本PTPRD和PD-L1 mRNA的表达，分析两者的相关性。采用蛋白质印迹法（Western blot）检测过表达或沉默PTPRD对PD-L1、STAT3和p-STAT3蛋白水平的影响。采用RTFQ-PCR检测PTPRD过表达对PD-L1转录水平的影响。结果：肝癌组织中PTPRD的表达显著低于癌旁组织（P＜0.05），PD-L1表达显著高于癌旁组织（P＜0.05），两者表达呈负相关性（r

=0.275 8，P=0.036 7）；PTPRD过表达时，PD-L1、STAT3和p-STAT3蛋白的表达水平下降（P＜0.05）

PTPRD沉默时，PD-L1的表达增高。结论：PTPRD和PD-L1表达水平在肝癌中呈负相关，PTPRD可能通过STAT3信号通路调节PD-L1的表达。PTPRD有望成为肝癌免疫治疗新靶点。

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 (P0.05)

while the expression of PD-L1 was significantly higher (P0.05).There was a negative correlation between PTPRD and PD-L1 expressions in hepatocellular carcinoma (r

=0.275 8

P=0.036 7). The protein expressions of PD-L1

STAT3 and p-STAT3 were down-regulated when PTPRD was overexpressed (P0.05)

while the expression level of PD-L1was increased in tissues with PTPRD knockdown (P0.05). 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 carci

noma.

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