Association Between Polymorphisms in Genes Encoding PD-1/PD-L1 Molecules and Clinicopathological Features in Clear...

Area of Science:

• Immunogenetics
• Oncology
• Molecular Biology

Background:

• The PD-1/PD-L1 pathway is vital for immune regulation but is often exploited by cancer cells to evade immune surveillance.
• Immune checkpoint inhibitors targeting the PD-1/PD-L1 axis are effective cancer therapies, highlighting the pathway's significance in tumor immunology.
• Understanding genetic variations within this pathway could reveal new biomarkers for cancer prognosis and treatment response.

Purpose of the Study:

• To investigate the association between single nucleotide polymorphisms (SNPs) in the PDCD1 (encoding PD-1) and CD274 (encoding PD-L1) genes with clinicopathological features, PD-L1 expression, and clinical outcomes in clear cell renal cell carcinoma (ccRCC).

Main Methods:

• Genotyping of four SNPs (rs11568821, rs7603052 in PDCD1; rs4143815, rs17718883 in CD274) in 238 ccRCC patients using TaqMan allelic discrimination assays.
• Analysis of associations between SNPs, PD-L1 immunohistochemical expression in tumor-infiltrating immune cells (TIICs) and tumor cells, and patient survival data.

Main Results:

• The PDCD1 rs7603052 polymorphism and CD274 rs17718883 polymorphism were significantly associated with PD-L1 expression in TIICs (p=0.033 and p=0.043, respectively).
• The CD274 rs4143815 polymorphism correlated with PD-L1 positivity in tumor cells (p=0.039).
• The CD274 rs17718883 polymorphism was a significant prognostic marker, with T allele carriers showing improved overall survival in ccRCC patients (p < 0.001).

Conclusions:

• Specific SNPs in PDCD1 and CD274 genes are associated with PD-L1 expression and clinical outcomes in ccRCC.
• These genetic variations may serve as valuable predictive and prognostic biomarkers for ccRCC patients.
• Further research is warranted to validate these findings and explore their clinical utility in personalized ccRCC treatment strategies.