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通过颗粒状模式、生长抑素受体 2 和 5 及 E-钙黏蛋白的表达预测肢端肥大症的治疗反应。

Predicting Response to Medical Treatment in Acromegaly via Granulation Pattern, Expression of Somatostatin Receptors Type 2 and 5 and E-Cadherin.

机构信息

Doctoral School of Medicine and Pharmacy, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Targu Mures, 540142 Targu Mures, Romania.

Department of Endocrinology, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Targu Mures, 540142 Targu Mures, Romania.

出版信息

Int J Mol Sci. 2024 Aug 8;25(16):8663. doi: 10.3390/ijms25168663.

Abstract

Resistance to first-generation somatostatin receptor ligand (fgSRL) treatment in acromegaly is common, making the identification of biomarkers that predict fgSRL response a desired goal. We conducted a retrospective analysis on 21 patients with acromegaly who underwent surgery and subsequent pharmacological treatment. Through immunohistochemistry (IHC), we assessed the expression of the somatostatin receptor subtypes SSTR2 and SSTR5, E-Cadherin, and cytokeratin granulation pattern (sparsely or densely). Patients were divided into responders and non-responders based on their biochemical response to fgSRL and/or the newer agent, Pasireotide, or the GH-blocker, Pegvisomant. Patients resistant to fgSRL (n = 12) exhibited lower SSTR2 and E-Cadherin expressions. Sparsely granulated tumors were more frequent in the non-responder group. SSTR2 ( = 0.024, r = 0.49) and E-Cadherin ( = 0.009, r = 0.64) positively correlated with the Insulin-like Growth Factor 1 (IGF-1) decrease after fgSRL, while SSTR5 ( = 0.107, r = -0.37) showed a trend towards negative correlation. SSTR5 positivity seemed to be associated with Pasireotide response, albeit the number of treated patients was too low (n = 4). No IHC markers correlated with Pegvisomant response. Our findings suggest that densely granulated tumors, with positive SSTR2 and E-Cadherin seem to be associated with favorable fgSRL responses. The strongest predictive value of the studied markers was found for E-Cadherin, which seems to surpass even SSTR2.

摘要

在肢端肥大症中,第一代生长抑素受体配体(fgSRL)治疗的耐药性很常见,因此,确定预测 fgSRL 反应的生物标志物是一个理想的目标。我们对 21 例接受手术和随后药物治疗的肢端肥大症患者进行了回顾性分析。通过免疫组织化学(IHC),我们评估了生长抑素受体亚型 SSTR2 和 SSTR5、E-钙黏蛋白和细胞角蛋白颗粒模式(稀疏或密集)的表达。根据患者对 fgSRL 和/或新型药物帕瑞肽或 GH 阻滞剂培维索孟的生化反应,将患者分为应答者和无应答者。对 fgSRL 耐药的患者(n = 12)表现出较低的 SSTR2 和 E-钙黏蛋白表达。稀疏颗粒的肿瘤在无应答组中更为常见。SSTR2( = 0.024,r = 0.49)和 E-钙黏蛋白( = 0.009,r = 0.64)与 fgSRL 后胰岛素样生长因子 1(IGF-1)的降低呈正相关,而 SSTR5( = 0.107,r = -0.37)呈负相关趋势。尽管接受治疗的患者数量太少(n = 4),但 SSTR5 阳性似乎与帕瑞肽的反应有关。没有免疫组织化学标志物与培维索孟的反应相关。我们的研究结果表明,密集颗粒的肿瘤,SSTR2 和 E-钙黏蛋白阳性似乎与 fgSRL 的良好反应相关。在研究的标志物中,E-钙黏蛋白的预测价值最强,似乎甚至超过 SSTR2。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f2b4/11354630/ab130a1b5b9f/ijms-25-08663-g001.jpg

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