Proteomic profiling of somatotropinoma subtypes reveals TNIP1 overexpression in sparsely granulated tumors in a small discovery cohort.

Authors

Vaishali Kaur, Debajyoti Chatterjee, Sanja Medenica, Apinderpreet Singh, Ashley B Grossman, Ashutosh Rai, Pinaki Dutta

Published in

Pituitary. Volume 29. Issue 6. Oct 25, 2026. Epub Oct 25, 2026.

Abstract

The molecular mechanisms underlying the clinical differences between densely granulated (DG) and sparsely granulated (SG) somatotroph tumors remain poorly understood. To identify significant molecular differences between these subtypes, we performed quantitative mass spectrometry-based proteomic profiling followed by validation of the differentially-identified proteins.
Label-free quantitative proteomic analysis was performed on SG somatotroph adenomas (SGSAs, n = 3) and DG somatotroph adenomas (DGSAs, n = 3), with each sample analyzed in technical triplicate. Key findings were subsequently validated using immunohistochemistry (IHC, n = 64), immunofluorescence (IF, n = 24), and Western blotting (WB, n = 18).
Proteomic profiling identified TNFAIP3-interacting protein 1 (TNIP1) as the most significantly over-expressed protein, and coenzyme Q6 monooxygenase (COQ6) as the most significantly under-expressed protein, in SGSAs compared with DGSAs. Higher TNIP1 expression in SGSAs was significantly associated with IGF-1 [%ULN], larger tumor diameter, greater tumor volume, higher Knosp grade and SSTR5 expression. In contrast, COQ6 expression showed significant negative correlations with tumor diameter, tumor volume, Knosp grade, and SSTR5 expression. These findings indicate strong associations between TNIP1 and COQ6 expression and tumor characteristics, along with differences in cell adhesion and signaling pathways.
SGSAs and DGSAs exhibit distinct proteomic profiles. Increased TNIP1 and reduced COQ6 expression, together with alterations in cell adhesion and signaling pathways in SGSA, may contribute to the molecular and phenotypic differences underlying these somatotroph tumor subtypes.

PMID:
42927587
Bibliographic data and abstract were imported from PubMed on 26 Oct 2026.

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