Yang Yingying, Babayan Lilit, Mirzakhanian Argishty, Sisliyan Nvard, Zhang Dongyun, Hurtado Carolina, Zahid Abdul, Bergsneider Marvin, Kim Won, Wang Marilene B, Heaney Anthony P
Departments of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Departments of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
Heliyon. 2023 Jan 4;9(1):e12678. doi: 10.1016/j.heliyon.2022.e12678. eCollection 2023 Jan.
FK506 binding protein 51 (FKBP5) is a co-chaperone regulator of the glucocorticoid receptor (GR). Recent studies have reported increased FKBP5 mRNA in the circulation from patients with Cushing disease (CD) which returned to comparable levels seen in healthy controls following successful -nasal -sphenoidal (TNTS) surgical corticotroph tumor removal. However, the expression of circulating FKBP5 mRNA levels in other pituitary tumor subtypes and its specificity to corticotroph tumors is unknown.
Pre-operative blood was collected from consecutive patients undergoing TNTS for pituitary tumors (n = 57) at our center between 2015 and 2019. Total RNA was isolated from whole blood using RiboPure blood RNA isolation kit and real-time qPCR was used to quantitate circulating FKBP5 mRNA expression.
Consistent with the prior report, higher circulating FKBP5 mRNA levels were observed in 20 patients with CD prior to surgical tumor removal, compared to 21 healthy controls (p < 0.0005) and compared to 8 patients harboring gonadotroph pituitary tumors (p < 0.05) and 6 patients with silent corticotroph pituitary tumors (p < 0.05). However, circulating FKBP5 mRNA levels were higher in 10 patients with prolactin (PRL)-secreting pituitary tumors compared to healthy controls (p < 0.05), and did not differ between patients with CD and patients with growth hormone secreting tumors (GH-omas).
Although we confirm that circulating FKBP5 mRNA is higher in patients with corticotroph tumors compared to healthy subjects, measurement of circulating FKBP5 does not appear to be helpful to distinguish corticotroph tumors from other pituitary tumor sub-types.
FK506结合蛋白51(FKBP5)是糖皮质激素受体(GR)的一种共伴侣调节因子。最近的研究报道,库欣病(CD)患者循环中的FKBP5 mRNA水平升高,在经蝶窦(TNTS)手术成功切除促肾上腺皮质激素肿瘤后,其水平恢复到健康对照者的可比水平。然而,循环中FKBP5 mRNA水平在其他垂体肿瘤亚型中的表达及其对促肾上腺皮质激素肿瘤的特异性尚不清楚。
2015年至2019年期间,在我们中心对连续接受TNTS治疗垂体肿瘤的患者(n = 57)术前采集血液。使用RiboPure血液RNA分离试剂盒从全血中分离总RNA,并使用实时定量PCR定量循环中FKBP5 mRNA的表达。
与先前的报道一致,在20例CD患者手术切除肿瘤前,观察到其循环中FKBP5 mRNA水平高于21例健康对照者(p < 0.0005),也高于8例促性腺激素垂体肿瘤患者(p < 0.05)和6例静止性促肾上腺皮质激素垂体肿瘤患者(p < 0.05)。然而,10例分泌催乳素(PRL)的垂体肿瘤患者的循环FKBP5 mRNA水平高于健康对照者(p < 0.05),CD患者与生长激素分泌肿瘤(GH瘤)患者之间的循环FKBP5 mRNA水平无差异。
虽然我们证实促肾上腺皮质激素肿瘤患者循环中的FKBP5 mRNA水平高于健康受试者,但检测循环中的FKBP5似乎无助于将促肾上腺皮质激素肿瘤与其他垂体肿瘤亚型区分开来。