Clinical impact of single nucleotide polymorphisms (SNPs) in <i>PDCD1</i> in patients with non-small cell lung cancer (NSCLC) receiving anti-PD1 immunotherapy.

Abstract

e20625 Background: Lung cancer is the leading cause of cancer-related deaths worldwide, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of all cases. Over the past few years, immunotherapy has emerged as a key treatment option for NSCLC, particularly targeting the PD-1/PD-L1 pathway. Although current biomarkers have significantly improved the treatment of NSCLC, the need for additional biomarkers remains critical. The identification of genetic variations, such as single nucleotide polymorphisms (SNPs) in PDCD1 gene, has gained attention due to their potential prognostic and predictive value. These SNPs may provide valuable information regarding treatment response, side effects, and overall survival in patients undergoing anti-PD1 therapy. In the current study we investigated the clinical significance of specific SNPs in PDCD1 gene and their impact on treatment outcomes in NSCLC patients receiving anti-PD1 immunotherapy. Methods: For this purpose, we studied the polymorphisms rs2227981 (PD1.5) and rs7421861 (PD1.7).The selection of the specific SNPs was based mostly on literature. Blood samples from 90 patients with stage III and IV NSCLC treated with anti-PD1 immunotherapy in the University Hospital of Patras were used. DNA was extracted and utilized for genotyping using Real-Time PCR with appropriate primers and labeled probes. Sanger sequencing was subsequently performed for specific samples for additional confirmation of the results. The genotypes frequencies were correlated with the clinicopathological characteristics and clinical outcomes of the patients. Finally, data analysis was carried out using the statistical software SPSS 28.0. Results: Interestingly, the rs7421861 polymorphism and especially the allele A, was associated with fewer irAEs (Immune-Related Adverse Events) ( p =0.021). In addition, A allele of rs7421861 was also associated with longer time to disease progression (TPP) and longer overall survival (OS, p =0.041 and p =0.003, respectively). On the other hand, no association was found between rs2227981 with the clinical outcome of the patients, however, this polymorphism was associated with the disease stage, specifically the AG genotype with stage III (p=0.016). Conclusions: Our study suggests that the single nucleotide polymorphism rs2227981 may, in the future, be used as prognostic and predictive biomarkers for patients with NSCLC receiving anti-PD1 immunotherapy, however more studies are needed to further validate its clinical significance.