Proteomic Profiles Associated With Postsurgical Progression in Nonfunctioning Pituitary Adenomas

Abstract

Context There is a lack of reliable biomarkers capable of predicting postoperative tumor progression of non-functioning pituitary adenomas (NFPAs). Objective To discover proteomic profiles associated with postoperative tumor progression in patients with NFPA. Design Case-controlled exploratory study. Setting Tertiary university hospital. Patients Tissue samples were obtained from 46 patients with residual tumor following surgery for NFPA 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). Intervention None. Main Outcome Measure Differentially expressed proteins (DEPs) between patient groups. Results Global quantitative proteomic analysis identified 4074 proteins, of which 550 were differentially expressed between the two groups (fold change>80%, false discovery rate-adjusted P≤0.05). PCA showed good separation between the two 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. Conclusions This is the first exploratory study analyzing proteomic profiles as markers of postoperative tumor progression in NFPA. 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 NFPA.

Over-expression of KRT8 is associated with invasion of non-functioning pituitary adenomas

“…The complete clinical excision of benign tumors, particularly due to their larger size, presents signi cant challenges as it may entail the risk of damaging surrounding vital structures. Postoperative radiotherapy may reduce residual tumor burden in some cases 8 .However, it is associated with the potential for severe pituitary function impairment, optic nerve damage, cognitive dysfunction and other complications, signi cantly impacting patients quality of life 9 .The management of invasive NFPAs through surgical and radiation therapy remains challenging, compounded by the lack of effective pharmacological interventions 10 . Therefore, there is a growing focus on identifying targeted therapeutic agents aimed at inhibiting the growth of non-functional pituitary adenomas by investigating invasion-related molecular markers.…”