Proteomic Profiles Associated With Postsurgical Progression in Nonfunctioning Pituitary Adenomas

• Published in: The journal of clinical endocrinology and metabolism 2024-05, Vol.109 (6), p.1485-1493
• Main Authors: Hallén, Tobias, Johannsson, Gudmundur, Thorsell, Annika, Olsson, Daniel S, Örndal, Charlotte, Engvall, Angelica, Jacobson, Frida, Widgren, Anna, Bergquist, Jonas, Skoglund, Thomas
• Format: Article
• Language: English
• Subjects: Adenoma; Adenoma - metabolism; Adenoma - pathology; Adenoma - surgery; Adult; Aged; Biomarkers, Tumor - analysis; Biomarkers, Tumor - metabolism; Case-Control Studies; Clinical; Disease Progression; Energy metabolism; Exploratory behavior; Female; Gene set enrichment analysis; Humans; Male; Metabolism; Middle Aged; mRNA; Neoplasm, Residual - pathology; nonfunctioning pituitary adenoma; Patients; Pituitary; Pituitary (anterior); Pituitary Neoplasms - metabolism; Pituitary Neoplasms - pathology; Pituitary Neoplasms - surgery; Principal components analysis; Proteins; Proteome - analysis; Proteome - metabolism; Proteomics; quantitative proteomics; reintervention; Robo protein; tumor progression; Tumors
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/clinem/dgad767

Abstract Context There is a lack of reliable biomarkers capable of predicting postoperative tumor progression of nonfunctioning pituitary adenomas (NFPAs). Objective To discover proteomic profiles associated with postoperative tumor progression in patients with NFPAs. This was a case-controlled exploratory study at a tertiary university hospital. Tissue samples were obtained from 46 patients with residual tumor following surgery for NFPAs of gonadotroph lineage. Two patient groups were compared: patients requiring reintervention due to residual tumor progression (cases; reintervention group, n = 29) and patients with a residual tumor showing no progression for a minimum of 5 years (controls; radiologically stable group, n = 17). Differentially expressed proteins (DEPs) between patient groups were measured. Results Global quantitative proteomic analysis identified 4074 proteins, of which 550 were differentially expressed between the 2 groups (fold change >80%, false discovery rate–adjusted P ≤ .05). Principal component analysis showed good separation between the 2 groups. Functional enrichment analysis of the DEPs indicated processes involving translation, ROBO-receptor signaling, energy metabolism, mRNA metabolism, and RNA splicing. Several upregulated proteins in the reintervention group, including SNRPD1, SRSF10, SWAP-70, and PSMB1, are associated with tumor progression in other cancer types. Conclusion This is the first exploratory study analyzing proteomic profiles as markers of postoperative tumor progression in NFPAs. The findings clearly showed different profiles between tumors with indolent postoperative behavior and those with postoperative tumor progression. Both enriched pathways involving DEPs and specific upregulated proteins have previously been associated with tumor aggressiveness. These results suggest the value of proteomic profiling for predicting tumor progression in patients with NFPAs.