Exploring the causal relationship between CX3CL1 and prostate cancer prognosis using Mendelian randomization

Area of Science:

• Oncology and Immunology
• Genetic Epidemiology
• Molecular Biology

Background:

• Prostate cancer (PCa) is a leading male cancer globally, with unknown causes complicating treatment.
• Emerging evidence suggests a link between immune responses, inflammation, and PCa development.
• This research investigates the role of inflammatory mediators, specifically CX3CL1, in PCa.

Purpose of the Study:

• To determine the causal relationship between CX3CL1 genetic variants and prostate cancer risk.
• To explore the association of CX3CL1 expression with PCa tumor characteristics and patient prognosis.
• To evaluate CX3CL1 as a potential biomarker for PCa risk and therapeutic target.

Main Methods:

• Genome-wide association study (GWAS) identified single-nucleotide polymorphisms (SNPs) linked to CX3CL1 expression.
• Two-sample Mendelian randomization (MR) and meta-analysis assessed the causal effect of CX3CL1 on PCa risk using large GWAS datasets.
• Gene expression, immune cell infiltration, survival analysis, and single-cell sequencing data were utilized to investigate CX3CL1's functional impact.

Main Results:

• Mendelian randomization and meta-analysis revealed an inverse causal association between CX3CL1 levels and PCa risk.
• CX3CL1 expression was significantly downregulated in PCa tissues and positively correlated with immune cell infiltration.
• Lower CX3CL1 expression correlated with poorer PCa patient prognosis and was markedly reduced in cancer cells.

Conclusions:

• Genetically predicted higher CX3CL1 levels are associated with reduced prostate cancer risk.
• Reduced CX3CL1 expression in PCa cells is linked to decreased immune infiltration and worse outcomes.
• CX3CL1 shows potential as a biomarker for PCa risk and prognosis, and as a target for immunotherapy.