晚期肝癌患者信号转导子和激活子3、微小核糖核苷酸-200表达与程序性细胞死亡配体1关联性及在程序性细胞死亡配体1抑制剂抵抗中的作用

摘要/Abstract

摘要： 目的: 探讨肝癌患者信号转导子和激活子3（STAT3）、微小核糖核苷酸-200（miR-200）表达与程序性细胞死亡配体1（PD-L1）关联性及在PD-L1抑制剂抵抗中的作用。
方法: 根据入组标准选取2019年2月至2022年1月承德市中心医院收治的108例晚期肝癌患者,根据治疗反应性分为抵抗组75例、非抵抗组33例。比较两组肝癌组织STAT3 mRNA、miR-200、PD-L1表达情况,并比较不同PD-L1表达水平患者肝癌组织STAT3 mRNA、miR-200表达情况。以Pearson法分析STAT3 mRNA、miR-200的关系及与PD-L1关系。以二元Logistic回归分析PD-L1抑制剂抵抗的相关影响因素。使用交互作用系数γ分析STAT3 mRNA、miR-200的交互作用是否存在及其作用类型。
结果: 抵抗组肝癌组织STAT3 mRNA、PD-L1表达高于非抵抗组,miR-200表达低于非抵抗组,差异均有统计学意义（均P<0.05）;PD-L1强表达患者STAT3 mRNA高于PD-L1低表达患者,而miR-200低于PD-L1低表达患者,差异均有统计学意义（均P<0.05）。STAT3 mRNA与miR-200呈负相关（P<0.05）,与PD-L1呈正相关（P<0.05）;miR-200与PD-L1呈负相关（P<0.05）。STAT3 mRNA、PD-L1是PD-L1抑制剂抵抗的相关危险因素,miR-200是PD-L1抑制剂抵抗的相关保护因素（均P<0.05）。单独STAT3 mRNA升高所致OR=21.000,单独miR-200降低所致OR=7.875,两者共存时所致OR=468.00;交互作用OR值大于单独STAT3 mRNA升高所致的OR值与单独miR-200降低所致OR值的乘积。STAT3 mRNA和miR-200对PD-L1抑制剂抵抗影响的模型为超相乘模型,γ=2.019>1,说明两者具有正向交互作用。
结论: 肝癌患者中STAT3表达升高,与PD-L1呈正相关;miR-200表达降低,与PD-L1呈负相关。STAT3、miR-200表达水平与PD-L1抑制剂抵抗密切相关,具有作为治疗靶点的潜在价值,并能为PD-L1抑制剂的精准化、个性化应用提供参考。

关键词: 肝癌, STAT3, miR-200, 程序性细胞死亡配体1, 程序性细胞死亡配体1抑制剂抵抗

Abstract: Objective:To investigate the correlation between the expression of signal transducer and activator 3 (STAT3), microribonucleotide-200 (miR-200) and programmed cell death-ligand 1 (PD-L1) in patients with liver cancer and its role in resistance to PD-L1 inhibitory.
Methods:From February 2019 to January 2022, a total of 108 patients with advanced liver cancer who were treated in Chengde central hospital were selected according to the enrollment criteria. They were divided into a resistance group(n=75) and a non-resistance group(n=33) according to their response to treatment. The expressions of STAT3 mRNA, miR-200 and PD-L1 in the two groups were compared, and compared the expressions of STAT3 mRNA and miR-200 in tissues of patients with different PD-L1 expression levels. Pearson was used to analyze the relationship between STAT3 mRNA, miR-200 and PD-L1, and binary Logistic regression was used to analyze the resistance to PD-L1 inhibitory. Related influencing factors, the interaction coefficient γ was used to analyze the existence and type of interaction between STAT3 mRNA and miR-200.
Results:The expression of STAT3 mRNA and PD-L1 in the resistance group was higher than that in the non-resistance group, and the miR-200 was lower than that in the non-resistance group, and the differences were statistically significant (all P<0.05). The STAT3 mRNA in patients with strong PD-L1 expression was higher than that in patients with low PD-L1 expression, and the miR-200 was lower than that in patients with low PD-L1 expression, and the difference was statistically significant (all P<0.05). Pearson correlation analysis showed that STAT3 mRNA was negatively correlated with miR-200 (P<0.05). STAT3 mRNA was positively correlated with PD-L1 (P<0.05), and miR-200 was negatively correlated with PD-L1 (P<0.05) . Logistic regression analysis showed that STAT3 mRNA and PD-L1 were related risk factors for PD-L1 inhibitory resistance, and miR-200 was a related protective factor for PD-L1 inhibitory resistance (all P<0.05). The interaction analysis showed that the OR value caused by the increase of STAT3 mRNA alone was 21.000, the OR value caused by the decrease of miR-200 alone was 7.875, and the OR value caused by the coexistence of the two was 468.00. The OR value of the interaction > STAT3 alone the product of the OR value caused by the increase of mRNA and the OR value caused by the decrease of miR-200 alone. The model was a hypermultiplicative model with γ =2.019> 1 for the effect of STAT3 mRNA and miR-200 on PD-L1 inhibitor resistance and indicating a positive interaction.
Conclusions:The expression of STAT3 in patients with liver cancer is increased, which is positively correlated with PD-L1. The expression of miR-200 is decreased, and the expression of miR-200 is negatively correlated with PD-L1. The expression levels of STAT3 and miR-200 are closely related to PD-L1 inhibitory resistance, and have potential as therapeutic targets the potential value of the point, and can provide a reference for the precise and personalized application of PD-L1 inhibitors.

Key words: Liver cancer, STAT3, miR-200, Programmed cell death-ligand1, PD-L1 inhibitory

刘少卿, 齐曼. 晚期肝癌患者信号转导子和激活子3、微小核糖核苷酸-200表达与程序性细胞死亡配体1关联性及在程序性细胞死亡配体1抑制剂抵抗中的作用[J]. 肝癌电子杂志, 2023, 10(4): 55-59.

Liu Shaoqing, Qi Man. Correlation of STAT3 and miR-200 expression with programmed cell death-ligand 1(PD-L1) in liver cancer patients and their role in resistance to PD-L1 inhibitory[J]. Electronic Journal of Liver Tumor, 2023, 10(4): 55-59.

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