Cushing’s Disease Manifestation in USP8-Mutated Corticotropinoma May Be Mediated by Interactions Between WNT Signaling and SST Trafficking
Abstract
:1. Introduction
2. Results
2.1. Clinical Data
2.2. USP8 Mutations Spectrum in Patients with Cushing’s Disease
2.3. Associations Between Somatic USP8 Mutation and Clinical Parameters
2.4. SST2/SST5 Expression and USP8 Mutation Status
2.5. Transcriptome Analysis of Pituitary Adenomas Harboring USP8-Mutant or USP8-WT in Patients with Cushing’s Disease
3. Discussion
4. Materials and Methods
4.1. Study Population of Patients with Cushing’s Disease
4.1.1. Hormone Measurements
4.1.2. Pituitary Magnetic Resonance Imaging
4.1.3. Immunnohistochemical (IHC) Staining
4.1.4. Statistical Analysis
4.2. DNA/RNA Purification from Tumor Samples
4.3. Sanger Sequencing of USP8
4.4. Transcriptome Sequencing and Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Clinical Data | USP8-Mutant | USP8-WT | p |
---|---|---|---|
Sex, m/f, % | 6%/94% | 24%/76% | p = 0.001 |
Age, years Me [25%; 75%] (min.–max.) | 36.5 [29; 56.5] (18–67) | 45 [34; 54] (21–60) | p = 0.43 |
Microadenomas/macroadenomas, % | 44%/56% | 29%/71% | p = 0.04 |
Maximum adenoma size, mm Me [25%; 75%] (min.–max.) | 11.25 [8; 15] (3–18) | 12 [6; 30] (4–49) | p = 0.21 |
Adenoma volume, mL Me [25%; 75%] (min.–max.) | 0.27 [0.1; 0.43] (0.003–1.56) | 0.37 [0.043; 6.23] (0.01–42.34) | p = 0.25 |
Morning plasma ACTH *, pg/mL Me [25%; 75%] (min.–max.) | 61.57 [50.56; 81.76] (23.54–128.3) | 82.99 [45.67; 161.2] (15.34–645.6) | p = 0.39 |
Morning serum cortisol *, nmol/L Me [25%; 75%] (min.–max.) | 735 [588.2; 837.3] (448–1094) | 638.85 [430.1; 831.6] (261–1690) | p = 0.51 |
24 h UFC *, nmol/24 h Me [25%; 75%] (min.–max.) | 492.5 [271.3–696.6] (137.88–1752) | 570 [195.8; 861.8] (56.8–3392) | p = 0.93 |
Ki67, % | 1 [0.4; 3.27] (0.1–5.3) | 1.47 [0.53; 3.64] (0.1–17.0) | p = 0.6 |
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Nerubenko, E.; Ryazanov, P.; Kuritsyna, N.; Paltsev, A.; Ivanova, O.; Grineva, E.; Kostareva, A.; Dmitrieva, R.; Tsoy, U. Cushing’s Disease Manifestation in USP8-Mutated Corticotropinoma May Be Mediated by Interactions Between WNT Signaling and SST Trafficking. Int. J. Mol. Sci. 2024, 25, 12886. https://doi.org/10.3390/ijms252312886
Nerubenko E, Ryazanov P, Kuritsyna N, Paltsev A, Ivanova O, Grineva E, Kostareva A, Dmitrieva R, Tsoy U. Cushing’s Disease Manifestation in USP8-Mutated Corticotropinoma May Be Mediated by Interactions Between WNT Signaling and SST Trafficking. International Journal of Molecular Sciences. 2024; 25(23):12886. https://doi.org/10.3390/ijms252312886
Chicago/Turabian StyleNerubenko, Elena, Pavel Ryazanov, Natalia Kuritsyna, Artem Paltsev, Oksana Ivanova, Elena Grineva, Anna Kostareva, Renata Dmitrieva, and Uliana Tsoy. 2024. "Cushing’s Disease Manifestation in USP8-Mutated Corticotropinoma May Be Mediated by Interactions Between WNT Signaling and SST Trafficking" International Journal of Molecular Sciences 25, no. 23: 12886. https://doi.org/10.3390/ijms252312886
APA StyleNerubenko, E., Ryazanov, P., Kuritsyna, N., Paltsev, A., Ivanova, O., Grineva, E., Kostareva, A., Dmitrieva, R., & Tsoy, U. (2024). Cushing’s Disease Manifestation in USP8-Mutated Corticotropinoma May Be Mediated by Interactions Between WNT Signaling and SST Trafficking. International Journal of Molecular Sciences, 25(23), 12886. https://doi.org/10.3390/ijms252312886