Genetic predictors of pituitary adenoma invasiveness in females: Insights from CXCL12 polymorphisms

Background. Pituitary adenoma (PA) is one of the most common brain tumours, yet its pathogenesis remains unclear [1]. PA varies in invasiveness; some remain confined to the pituitary gland, while others aggressively infiltrate surrounding tissues, leading to more severe clinical complications [2]. Molecular biomarkers indicate biological and pathological processes or therapeutic responses, offering valuable insights for diagnosis and prognosis [3]. CXCL12, a homeostatic chemokine, induces migration and activation of haematopoietic progenitors, endothelial cells, and leukocytes, regulating the tumour microenvironment by promoting angiogenesis and immune cell recruitment, potentially aiding tumour growth [4]. Polymorphisms within the CXCL12 gene, particularly those influencing its expression or function, may affect PA susceptibility, tumour size, invasiveness, and response to treatment [5]. A deeper understanding of the genetic mechanisms underlying CXCL12 may contribute to developing personalised therapeutic approaches and enhancing prognostic tools for PA management. Aim. The current study aimed to investigate the associations between the CXCL12 rs1801157, rs2297630 polymorphisms, and the PA invasiveness in females. Methods. A case-control study enrolled 90 females with PA and 160 healthy females. DNA samples from peripheral blood leukocytes were purified by the DNA salting-out method. Single nucleotide polymorphisms (rs1801157, rs2297630) were determined using real-time polymerase chain reaction (RT-PCR). The results were analysed using the IBM SPSS Statistics 29.1 statistical analysis method. Results. We found that CXCL12 rs1801157 TT genotype and T allele were statistically significantly more frequent in the non-invasive PA group compared to control group females (8.7 vs. 2.5, p = 0.043, 28.3 vs 16.9, p = 0.014, respectively). In the invasive PA group, it was found that CXCL12 rs2297630 AA genotype and A allele were statistically significantly more frequent in the control group than in the invasive PA group females (8.1 vs. 0, p = 0.009, 29.7 vs. 13.6, p = 0.002, respectively). A binary logistic regression analysis evaluated the impact of CXCL12 rs1801157 and rs2297630 on non-invasive/invasive PA development. The analysis revealed that CXCL12 rs1801157 T allele increased the odds of non-invasive PA’s development 1.9.-fold under the additive model (OR: 1.951, CI: 1.124–3.386, p = 0.018). Moreover, the CXCL12 rs2297630 A allele decreases the odds of invasive PA development 2.8-fold under the additive model (OR: 0.359, CI: 0.183–0.705, p = 0.003). Conclusions. The CXCL12 rs2297630 A allele suggests a potential protective effect against invasive PA development. In contrast, the CXCL12 rs1801157 T allele may be a risk factor for developing non-invasive forms of PA.