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垂体腺瘤:rs2236750、rs34037914 和 rs267606574 遗传变异、血清水平与 Ki-67 标记指数的相关性。

Pituitary Adenoma: rs2236750, rs34037914, and rs267606574 Genetic Variants, Serum Levels, and Ki-67 Labeling Index Associations.

机构信息

Neuroscience Institute, Medical Academy, Lithuanian University of Health Sciences, Eiveniu 2, 50161 Kaunas, Lithuania.

Latvian Biomedical Research and Study Centre (BMC), LV-1067 Rīga, Latvia.

出版信息

Medicina (Kaunas). 2024 Aug 1;60(8):1252. doi: 10.3390/medicina60081252.

DOI:10.3390/medicina60081252
PMID:39202532
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11356775/
Abstract

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. The investigation focuses on the Ki-67 labeling index, rs2236750, rs34037914, and 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. The results derived from binary logistic regression analysis revealed an intriguing correlation between the rs2236750 AG genotype and approximately a 1.6-fold increased likelihood of PA occurrence. When analyzing rs34037914, statistically significant differences were found between Micro-PA and the reference group ( = 0.022). Additionally, the 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. Consequently, while this study hinted at a potential link between rs2236750 and pituitary adenoma development, as well as a potential link between rs34037914 and Micro-PA development, it underscored the need for further analysis involving a larger cohort to robustly validate these findings.

摘要

这项研究探索了垂体腺瘤(PA)的复杂发病机制,PA 是垂体腺中常见的颅内肿瘤。尽管它们通常具有良性性质,但 PA 表现出广泛的临床谱,涉及激素分泌过多和不同程度的侵袭性,暗示了多方面的分子机制和肿瘤发生和基因调控中的异常。该研究重点关注 Ki-67 标记指数、rs2236750、rs34037914 和 rs267606574 多态性,以及 SSTR2、SSTR5 和 AIP 的血清水平,以辨别它们与 PA 的关联。Ki-67 标记指数通过使用单克隆抗体克隆 SP6 的免疫组织化学分析进行评估,代表显示阳性染色的肿瘤细胞的百分比。通过实时聚合酶链反应进行基因分型,通过 ELISA 分析血清水平。该研究包括 128 例 PA 患者和 272 例参考组受试者。二元逻辑回归分析得出的结果显示,rs2236750 AG 基因型与 PA 发生的可能性增加约 1.6 倍之间存在有趣的相关性。在分析 rs34037914 时,在 Micro-PA 和参考组之间发现了统计学上显著的差异( = 0.022)。此外,与 CC+CT 相比,在最稳健的遗传模型(基于最低 AIC 值选择)下,rs34037914 TT 基因型与 Micro-PA 发生的几率增加 12 倍相关。然而,值得注意的是,在应用 Bonferroni 校正后,这些发现不再具有统计学意义。因此,虽然这项研究暗示了 rs2236750 与垂体腺瘤发展之间存在潜在联系,以及 rs34037914 与 Micro-PA 发展之间存在潜在联系,但它强调需要进一步分析涉及更大的队列,以稳健验证这些发现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b42d/11356775/4c8c413aea25/medicina-60-01252-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b42d/11356775/56c35ca626f7/medicina-60-01252-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b42d/11356775/8b69a7ae4972/medicina-60-01252-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b42d/11356775/77a96cfa9856/medicina-60-01252-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b42d/11356775/4c8c413aea25/medicina-60-01252-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b42d/11356775/56c35ca626f7/medicina-60-01252-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b42d/11356775/8b69a7ae4972/medicina-60-01252-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b42d/11356775/77a96cfa9856/medicina-60-01252-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b42d/11356775/4c8c413aea25/medicina-60-01252-g004.jpg

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