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Proteogenomic landscape of uterine leiomyomas from hereditary leiomyomatosis and renal cell cancer patients.
- Source :
-
Scientific reports [Sci Rep] 2021 Apr 30; Vol. 11 (1), pp. 9371. Date of Electronic Publication: 2021 Apr 30. - Publication Year :
- 2021
-
Abstract
- Pathogenic mutations in fumarate hydratase (FH) drive hereditary leiomyomatosis and renal cell cancer (HLRCC) and increase the risk of developing uterine leiomyomas (ULMs). An integrated proteogenomic analysis of ULMs from HLRCC (n = 16; FH-mutation confirmed) and non-syndromic (NS) patients (n = 12) identified a significantly higher protein:transcript correlation in HLRCC (R = 0.35) vs. NS ULMs (R = 0.242, MWU p = 0.0015). Co-altered proteins and transcripts (228) included antioxidant response element (ARE) target genes, such as thioredoxin reductase 1 (TXNRD1), and correlated with activation of NRF2-mediated oxidative stress response signaling in HLRCC ULMs. We confirm 185 transcripts previously described as altered between HLRCC and NS ULMs, 51 co-altered at the protein level and several elevated in HLRCC ULMs are involved in regulating cellular metabolism and glycolysis signaling. Furthermore, 367 S-(2-succino)cysteine peptides were identified in HLRCC ULMs, of which sixty were significantly elevated in HLRCC vs. NS ULMs (LogFC = 1.86, MWU p < 0.0001). These results confirm and define novel proteogenomic alterations in uterine leiomyoma tissues collected from HLRCC patients and underscore conserved molecular alterations correlating with inactivation of the FH tumor suppressor gene.
- Subjects :
- Biomarkers, Tumor genetics
Biomarkers, Tumor metabolism
Case-Control Studies
Female
Humans
Leiomyomatosis metabolism
Neoplastic Syndromes, Hereditary metabolism
Proteome analysis
Skin Neoplasms metabolism
Uterine Neoplasms metabolism
Biomarkers, Tumor analysis
Fumarate Hydratase genetics
Genetic Predisposition to Disease
Leiomyomatosis pathology
Mutation
Neoplastic Syndromes, Hereditary pathology
Proteogenomics methods
Proteome metabolism
Skin Neoplasms pathology
Uterine Neoplasms pathology
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 11
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 33931688
- Full Text :
- https://doi.org/10.1038/s41598-021-88585-x