Genetic Predictors of Pituitary Adenoma Invasiveness and Activity: Insights from CXCL12 Variants

Introduction Pituitary adenoma (PA) is one of the most common brain tumors, yet its pathogenesis remains unclear (1). PA varies in invasiveness and activity, with some tumors remaining localized and others infiltrating surrounding tissues, causing severe complications. PA can also be hormone-secreting, leading to endocrine imbalances, or non-secreting, inducing pressure on nearby structures (2). Molecular biomarkers indicate biological and pathological processes or therapeutic responses, offering valuable insights for diagnosis and prognosis (3). CXCL12, a homeostatic chemokine, regulates the tumor microenvironment by promoting angiogenesis and immune cell recruitment, potentially supporting tumor growth (4). Variants within the CXCL12 gene, particularly those influencing its expression or function, may affect PA susceptibility, invasiveness, activity, and response to treatment (5). A deeper understanding of the genetic mechanisms underlying CXCL12 may contribute to developing personalized therapeutic approaches and enhancing prognostic tools for PA management. Aim To assess the association of CXCL12 gene variants rs1801157 and rs2297630 with pituitary adenoma invasiveness and hormonal activity. Methods A case-control study was conducted involving 390 subjects, divided into two groups: the control group (n = 240) and the PA group (n = 150). DNA samples from peripheral blood leukocytes were purified using the DNA salting-out method. Single nucleotide variants (rs1801157, rs2297630) were identified using real-time polymerase chain reaction (RTPCR). The results were analyzed using the IBM SPSS Statistics 30 software. Results We found that CXCL12 rs2297630 A allele was associated with a 1.6-fold decreased odds of PA occurrence under the additive model (OR = 0.618; CI: 0.436–0.876; p = 0.007). Also, CXCL12 rs2297630 A allele decreases the odds of invasive PA development by 1.9-fold under the additive and dominant models (OR: 0.518, CI: 0.324-0.828, p = 0.006; and OR: 0.527, CI: 0.306-0.911, p = 0.022, respectively). CXCL12 rs1801157 T allele increased the odds of active PA’s development by 1.6-fold and 1.7-fold under the additive and dominant models (OR: 1.666, CI: 1.089-2.546, p = 0.018; and OR: 1.781, CI: 1.079-2.939, p = 0.024, respectively). Moreover, the CXCL12 rs2297630 A allele decreases the odds of inactive PA development by 2.3-fold under the additive and dominant models (OR: 0.426, CI: 0.250-0.726, p = 0.002; and OR: 0.438, CI: 0.240-0.797, p = 0.007, respectively). Conclusions The CXCL12 rs2297630 A allele suggests a potential protective effect against PA occurrence and invasiveness, as well as lower odds of having an inactive PA. In contrast, the CXCL12 rs1801157 T allele may be a risk factor for developing more active forms of PA.