Programmed death-ligand 1 single nucleotide polymorphism affects breast cancer chemosensitivity and adverse events in the neoadjuvant setting

Abstract

Objective We aimed to determine whether single nucleotide polymorphisms in the PD-L1 gene are related to the response and adverse events of patients receiving neoadjuvant therapy and to explore the mechanism. Methods Nine single nucleotide polymorphisms of PD-L1 were selected and tested among patients before neoadjuvant therapy. Four models were used in single nucleotide polymorphism genotype analysis: the addictive model compared TT vs TA vs AA; the dominant model compared TT vs TA+AA; the recessive model compared TT+TA vs AA; and the over-dominant model compared TT+AA vs TA (A as the minor allele). We analyzed the associations between single nucleotide polymorphism genotypes and pathological complete response, disease-free survival, and adverse events. Overexpression of the targeted microRNA was carried out using microRNA mimics. Logistic regression was used to analyze the associations between different single nucleotide polymorphism genotypes and pathological complete response outcome. Kaplan–Meier plots and log-rank tests were used to compare disease-free survival between groups with different single nucleotide polymorphism genotypes. The Cox proportional hazards model was used to calculate the adjusted hazard ratio. The Spearman's correlation test was used to determine the correlations between different genotypes and adverse events. Results rs4143815C>G was associated with better pathological complete response in the addictive and over-dominant models and with poorer disease-free survival in the recessive model. Patients with different genotypes had different adverse events. Overexpression of miR34c resulted in the downregulation of PD-L1 mRNA expression. Conclusion The PD-L1 single nucleotide polymorphism rs4143815 was associated with the pathological complete response rate, disease-free survival, and adverse events in breast cancer patients receiving neoadjuvant therapy. The interaction between miR34c and PD-L1 might be affected by rs4143815.