Medicina (Aug 2024)

Pituitary Adenoma: <i>SSTR2</i> rs2236750, <i>SSTR5</i> rs34037914, and <i>AIP</i> rs267606574 Genetic Variants, Serum Levels, and Ki-67 Labeling Index Associations

  • Greta Gedvilaite-Vaicechauskiene,
  • Loresa Kriauciuniene,
  • Arimantas Tamasauskas,
  • Vita Rovite,
  • Ilona Mandrika,
  • Sheng-Nan Wu,
  • Chin-Wei Huang,
  • Lina Poskiene,
  • Rasa Liutkeviciene

DOI
https://doi.org/10.3390/medicina60081252
Journal volume & issue
Vol. 60, no. 8
p. 1252

Abstract

Read online

Background and Objectives: This study explores the complex pathogenesis of pituitary adenomas (PAs), prevalent intracranial tumors in the pituitary gland. Despite their generally benign nature, PAs exhibit a diverse clinical spectrum involving hormone hypersecretion and varying invasiveness, hinting at multifaceted molecular mechanisms and abnormalities in tumorigenesis and gene regulation. Materials and Methods: The investigation focuses on the Ki-67 labeling index, SSTR2 rs2236750, SSTR5 rs34037914, and AIP rs267606574 polymorphisms, alongside serum levels of SSTR2, SSTR5, and AIP, to discern their association with PAs. The Ki-67 labeling index was assessed using immunohistochemical analysis with the monoclonal antibody clone SP6, representing the percentage of tumor cells showing positive staining. Genotyping was performed via real-time polymerase chain reaction, and serum levels were analyzed using ELISA. The study included 128 PA patients and 272 reference group subjects. Results: The results derived from binary logistic regression analysis revealed an intriguing correlation between the SSTR2 rs2236750 AG genotype and approximately a 1.6-fold increased likelihood of PA occurrence. When analyzing SSTR5 rs34037914, statistically significant differences were found between Micro-PA and the reference group (p = 0.022). Additionally, the SSTR5 rs34037914 TT genotype, compared with CC + CT, under the most robust genetic model (selected based on the lowest AIC value), was associated with a 12-fold increased odds of Micro-PA occurrence. However, it is noteworthy that after applying Bonferroni correction, these findings did not retain statistical significance. Conclusions: Consequently, while this study hinted at a potential link between SSTR2 rs2236750 and pituitary adenoma development, as well as a potential link between SSTR5 rs34037914 and Micro-PA development, it underscored the need for further analysis involving a larger cohort to robustly validate these findings.

Keywords