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.

Programmed death-ligand 1 (PD-L1) polymorphisms as predictive biomarkers for the development of liver cirrhosis and hepatocellular carcinoma in HCV Egyptian patients

“…Yeo and his colleagues reported that the PD‐L1 rs4143815 GG genotype may be beneficial for predicting poor prognosis in lung adenocarcinoma as patients with this genotype had lower overall survival and disease-free survival compared to patients with other genotypes of PD-L1 rs4143815 [ 27 ]. As well, prior studies stated that the PD‐L1 rs4143815C > G was significantly associated with a worse survival outcome and relapse with NSCLC and breast cancer [ 10 , 28 , 29 ]. Furthermore, Lee et al [ 30 ] investigated whether the PD-L1 gene polymorphisms could predict the clinical outcome of patients with advanced NSCLC after paclitaxel-cisplatin chemotherapy and they found that the rs4143815 CG SNP was significantly associated with a better response under additive model for the G-allele.…”

A Tumor and Immune-Related Micro-RNA Signature Predicts Relapse-Free Survival of Melanoma Patients Treated with Ipilimumab

“…Importantly, TAP1 and HLA-A are essential components of T cell function, and high expression of these molecules was found to increase the survival probability of melanoma patients [23]. Moreover, since miRNA influences PD-L1 expression, immunotherapy with high expression of miR34c therefore results in the downregulation of PD-L1 mRNA expression in breast cancer [24].…”

Associação Do Polimorfismo Do Gene Ligante De Morte Programada-1 (Pd-L1) Com O Câncer De Mama

“…Mutações não codificantes de SNPs estão frequentemente associadas ao desenvolvimento de tumores. Atualmente, os estudos de SNPs têm se concentrado principalmente na codificação de SNPs (Lu et al, 2020).…”

“…Foi observado que, o SNP (rs4143815do) do gene PD-L1 foi associado à taxa de resposta patológica completa, sobrevida livre de doença e eventos adversos em pacientes com câncer de mama recebendo terapia neoadjuvante. Vários ensaios clínicos em larga escala confirmaram que os pacientes que atingem a resposta patológica completa em terapia neoadjuvante têm um prognóstico muito melhor do que pacientes sem resposta patológica completa (Lu et al, 2020).…”