Immunological Consequences of rs5742621 Variant and IGF-1 in Modulating MIF, IL-27, and CXCL12 Expression in Individuals with Prostate Cancer
TL;DR
The GA genotype of rs5742621 was significantly associated with elevated IGF-1 levels and increased PCa risk, promoting cell proliferation, inhibiting apoptosis, and accelerating tumor growth.
Abstract
Prostate cancer (PCa) is the second most common cancer among men worldwide. Immunological biomarkers play a crucial role in disease diagnosis, progression, and treatment. This study aimed to investigate the relationship between the rs5742621 (A>G) genetic variant and serum levels of insulin-like growth factor 1 (IGF-1) and other cytokines in patients with PCa compared to healthy controls. A total of 204 patients with PCa (aged 48–80) and 196 healthy controls were enrolled. Blood samples were collected to genotype the rs5742621 variant using the tetra-primer amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Serum levels of IGF1, macrophage migration inhibitory factor (MIF), CXC motif chemokine ligand 12 (CXCL12), and interleukin-27 (IL-27) were measured using a sandwich immunoassay. The heterozygous GA genotype of rs5742621 was more prevalent among patients with PCa, while the AA genotype was more prevalent in healthy controls. Additionally, serum IGF-1 levels were significantly elevated in PCa patients (median: 110 pg/mL) compared to healthy controls (median: 65 pg/mL; p < 0.001). Similarly, MIF levels were higher in PCa patients (85 pg/mL vs. 45 pg/mL; p < 0.001), as were CXCL12 concentrations (140 pg/mL vs. 40 pg/mL; p < 0.001). In contrast, IL-27 levels were lower in PCa patients (40 pg/mL) than in controls (65 pg/mL; p < 0.001). ROC curve analysis demonstrated that CXCL12 and MIF both achieved perfect diagnostic accuracy (AUC = 1.0), while IGF1 showed excellent diagnostic performance (AUC = 0.979) and IL-27 showed good performance (AUC = 0.903). The GA genotype of rs5742621 was significantly associated with elevated IGF-1 levels and increased PCa risk, promoting cell proliferation, inhibiting apoptosis, and accelerating tumor growth. IGF-1 and related immunological markers may serve as promising diagnostic biomarkers and potential therapeutic targets for prostate cancer.