A long-term prognosis study of human USP8-mutated ACTH-secreting pituitary neuroendocrine tumours

IF 3 3区医学 Q2 ENDOCRINOLOGY & METABOLISM

Clinical Endocrinology Pub Date : 2024-05-01 DOI:10.1111/cen.15065

Hui Miao, Luo Wang, Fengying Gong, Lian Duan, Linjie Wang, Yong Yao, Ming Feng, Kan Deng, Renzhi Wang, Yu Xiao, Qing Ling, Huijuan Zhu, Lin Lu

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引用次数: 0

Abstract

Objective

Somatic variants in the ubiquitin-specific protease 8 (USP8) gene are the most common genetic cause of Cushing disease. We aimed to explore the relationship between clinical outcomes and USP8 status in a single centre.

Design, patients and measurements

We investigated the USP8 status in 48 patients with pituitary corticotroph tumours. A median of 62 months of follow-up was conducted after surgery from November 2013 to January 2015. The clinical, biochemical and imaging features were collected and analysed.

Results

Seven USP8 variants (p.Ser718Pro, p.Ser719del, p.Pro720Arg, p.Pro720Gln, p.Ser718del, p.Ser718Phe, p.Lys713Arg) were identified in 24 patients (50%). USP8 variants showed a female predominance (100% vs. 75% in wild type [WT], p = .022). Patients with p.Ser719del showed an older age at surgery compared to patients with the p.Pro720Arg variant (47- vs. 24-year-olds, p = .033). Patients with p.Pro720Arg showed a higher rate of macroadenoma compared to patients harbouring the p.Ser718Pro variant (60% vs. 0%, p = .037). No significant differences were observed in serum and urinary cortisol and adrenocorticotropin hormone (ACTH) levels. Immediate surgical remission (79% vs. 75%) and long-term hormone remission (79% vs. 67%) were not significantly different between the two groups. The recurrence rate was 21% (4/19) in patients harbouring USP8 variants and 13% (2/16) in WT patients. Recurrence-free survival presented a tendency to be shorter in USP8-mutated individuals (76.7 vs. 109.2 months, p = .068).

Conclusions

Somatic USP8 variants accounted for 50% of the genetic causes in this cohort with a significant female frequency. A long-term follow-up revealed a tendency toward shorter recurrence-free survival in USP8-mutant patients.

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人类 USP8 突变的促肾上腺皮质激素分泌垂体神经内分泌肿瘤的长期预后研究

目的泛素特异性蛋白酶 8（USP8）基因的基因变异是库欣病最常见的遗传病因。我们对 48 例垂体促肾上腺皮质激素瘤患者的 USP8 状态进行了调查。2013年11月至2015年1月，我们对手术后进行了中位数为62个月的随访。结果在 24 名患者（50%）中发现了 7 个 USP8 变异（p.Ser718Pro、p.Ser719del、p.Pro720Arg、p.Pro720Gln、p.Ser718del、p.Ser718Phe、p.Lys713Arg）。USP8 变体显示女性占多数（100% 对野生型 [WT] 的 75%，p = .022）。与p.Pro720Arg变异体患者相比，p.Ser719del患者的手术年龄更大（47岁对24岁，p = .033）。与p.Ser718Pro变异体患者相比，p.Pro720Arg患者的大腺瘤发生率更高（60% 对 0%，p = .037）。血清和尿液中的皮质醇和促肾上腺皮质激素（ACTH）水平无明显差异。两组患者的近期手术缓解率（79% 对 75%）和长期激素缓解率（79% 对 67%）无明显差异。携带USP8变异体的患者复发率为21%（4/19），WT患者复发率为13%（2/16）。USP8变异个体的无复发生存期有缩短的趋势（76.7 个月 vs. 109.2 个月，p = .068）。长期随访显示，USP8变异患者的无复发生存期有缩短的趋势。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical Endocrinology 医学-内分泌学与代谢

CiteScore

6.40

自引率

3.10%

发文量

192

审稿时长

1 months

期刊介绍： Clinical Endocrinology publishes papers and reviews which focus on the clinical aspects of endocrinology, including the clinical application of molecular endocrinology. It does not publish papers relating directly to diabetes care and clinical management. It features reviews, original papers, commentaries, correspondence and Clinical Questions. Clinical Endocrinology is essential reading not only for those engaged in endocrinological research but also for those involved primarily in clinical practice.