Lineage-specific steroidomic signatures in pituitary neuroendocrine tumors: pregnenolone enrichment in SF-1 lineage and associations with tumor behavior
Endocrine-Related Cancer, cilt.33, sa.7, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 33 Sayı: 7
- Basım Tarihi: 2026
- Doi Numarası: 10.1530/erc-26-0154
- Dergi Adı: Endocrine-Related Cancer
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, EMBASE, MEDLINE, Academic Search Ultimate (EBSCO), Health Research Premium Collection (ProQuest)
- Anahtar Kelimeler: PitNET, cell lineage, SF-1 (steroidogenic factor 1), TPIT (T-box transcription factor), intratumoral steroids, pregnenolone
- Sağlık Bilimleri Üniversitesi Adresli: Evet
Özet
Pituitary neuroendocrine tumors (PitNETs) exhibit diverse biological behaviors, yet the metabolic determinants underlying lineage-specific characteristics remain poorly understood. This study characterized intratumoral steroid metabolite profiles in relation to transcription factor (TF)-defined lineages and radiological tumor features in 69 PitNET specimens obtained during transsphenoidal surgery between 2021 and 2023. Tumors were classified according to the WHO 2022 TF-based criteria (SF-1, PIT-1, and TPIT). Tissue concentrations of 14 steroid metabolites were quantified via liquid chromatography–tandem mass spectrometry, with associations evaluated using multivariable regression and partial least squares discriminant analysis (PLS-DA). Gonadotroph tumors (n = 34) exhibited marked pregnenolone (PREG) elevation compared with other lineages (median: 104.6 vs 1.2 ng/g, P < 0.001, ε2 = 0.38). Corticotroph tumors (n = 9) showed enrichment of glucocorticoid metabolites, particularly 11-deoxycortisol (adjusted P = 0.002, ε2 = 0.30), while PIT-1 tumors (n = 23) displayed intermediate levels. PLS-DA corroborated these patterns, with 11-deoxycortisol and pregnenolone emerging as the primary discriminators (68% total variance). Multivariable analysis confirmed SF-1 lineage to be independently associated with PREG levels after adjusting for clinical and radiological covariates (adjusted R2 = 0.56, P < 0.001). Inverse associations were observed between deoxycorticosterone/11-deoxycortisol and tumor expansion (r = -0.7 and r = -0.4, both P < 0.001), and PREG correlated with cavernous sinus invasion within gonadotroph tumors (P = 0.03). During follow-up (median: 32–38 months), steroid profiles showed no association with clinical outcomes. TF-defined PitNET lineages exhibit distinct intratumoral steroid profiles reflecting intrinsic metabolic properties of lineage-specific cell populations, revealing a novel metabolic dimension to PitNET biology.