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垂体腺瘤病理生理学中(rs351855和rs7708357)基因变异、Ki-67和p53的研究进展

Insights into (rs351855 and rs7708357) Gene Variants, Ki-67 and p53 in Pituitary Adenoma Pathophysiology.

作者信息

Juskiene Martyna, Duseikaite Monika, Vilkeviciute Alvita, Kariniauske Egle, Baikstiene Ieva, Makstiene Jurgita, Poskiene Lina, Tamasauskas Arimantas, Liutkeviciene Rasa, Verkauskiene Rasa, Zilaitiene Birute

机构信息

Institute of Endocrinology, Department of Endocrinology, Lithuanian University of Health Sciences, 50140 Kaunas, Lithuania.

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

出版信息

Int J Mol Sci. 2025 Aug 5;26(15):7565. doi: 10.3390/ijms26157565.

DOI:10.3390/ijms26157565
PMID:40806692
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12347107/
Abstract

To determine the association between (rs351855 and rs7708357) gene variants, serum levels, and immunohistochemical markers (Ki-67 and p53) in pituitary adenoma (PA), a case-control study was conducted involving 300 subjects divided into two groups: the control group ( = 200) and a group of PA ( = 100). The genotyping of rs351855 and rs7708357 was carried out using the real-time polymerase chain reaction (RT-PCR) method. The serum FGFR4 levels were measured using the ELISA method. Immunohistochemical analysis (Ki-67 and p53) was conducted. Statistical analysis of the data was performed using IBM SPSS Statistics 30.0 software. There were no statistically significant differences after analyzing the genotypes and alleles of rs351855 and rs7708357 in patients with PA and control groups (all > 0.05). After evaluating the distribution of genotypes and alleles of rs351855 and rs7708357 in micro/macro, invasiveness, activity, and recurrence of PA and the control groups, the analysis showed no statistically significant differences between the groups ( > 0.05). Similarly, no significant differences in FGFR4 levels were observed between PA patients and control group (median (IQR): 3642.41 (1755.08) pg/mL vs. 3126.24 (1334.15) pg/mL, = 0.121). Immunohistochemistry for Ki-67 revealed a labeling index (LI) of <1% in 25.5% of patients with PA, an LI of 1% in 10.9%, and an LI of >1% in 63.6% of patients. Further analyses showed no statistically significant associations with tumor size, invasiveness, activity, or recurrence. Immunohistochemistry for p53 revealed that macroadenomas had a significantly higher p53 H-score compared to microadenomas (median (IQR): 30.33 (28.68) vs. 18.34 (17.65), = 0.005). Additionally, a moderate, statistically significant positive correlation between the Ki-67 LI and the p53 expression was found (Spearman's ρ = 0.443, = 0.003, = 43). variants and serum protein levels were not significantly associated with PA risk or tumor features. Conversely, immunohistochemical markers Ki-67 and p53 were more informative, with higher p53 expression in macroadenomas and a moderate positive correlation between Ki-67 and p53, highlighting their potential relevance in tumor growth assessment.

摘要

为了确定垂体腺瘤(PA)中(rs351855和rs7708357)基因变异、血清水平与免疫组化标志物(Ki-67和p53)之间的关联,进行了一项病例对照研究,涉及300名受试者,分为两组:对照组(n = 200)和PA组(n = 100)。采用实时聚合酶链反应(RT-PCR)方法对rs351855和rs7708357进行基因分型。采用酶联免疫吸附测定(ELISA)方法测量血清FGFR4水平。进行免疫组化分析(Ki-67和p53)。使用IBM SPSS Statistics 30.0软件对数据进行统计分析。分析PA患者和对照组中rs351855和rs7708357的基因型和等位基因后,未发现统计学上的显著差异(所有P>0.05)。评估rs351855和rs7708357的基因型和等位基因在PA和对照组的微/大腺瘤、侵袭性、活性和复发中的分布后,分析显示两组之间无统计学显著差异(P>0.05)。同样,PA患者与对照组之间的FGFR4水平未观察到显著差异(中位数(四分位间距):3642.41(1755.08)pg/mL对3126.24(1334.15)pg/mL,P = 0.121)。Ki-67免疫组化显示,25.5%的PA患者标记指数(LI)<1%,10.9%的患者LI为1%,63.6%的患者LI>1%。进一步分析显示,与肿瘤大小、侵袭性、活性或复发无统计学显著关联。p53免疫组化显示,大腺瘤的p53 H评分显著高于微腺瘤(中位数(四分位间距):30.33(28.68)对18.34(17.65),P = 0.

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8dd/12347107/6396800983bd/ijms-26-07565-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8dd/12347107/62cbf9b1e173/ijms-26-07565-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8dd/12347107/306642ebc79b/ijms-26-07565-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8dd/12347107/11c8006dff61/ijms-26-07565-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8dd/12347107/6396800983bd/ijms-26-07565-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8dd/12347107/62cbf9b1e173/ijms-26-07565-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8dd/12347107/306642ebc79b/ijms-26-07565-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8dd/12347107/11c8006dff61/ijms-26-07565-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8dd/12347107/6396800983bd/ijms-26-07565-g004.jpg

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