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

Abstract

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

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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