Proteogenomic landscape of uterine leiomyomas from hereditary leiomyomatosis and renal cell cancer patients
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 FH tumor suppressor gene.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Apr 30, 2021
- Source ID
- 10.1038/s41598-021-88585-x
Entities
People
- Anthony R Soltis
- Ayman Al-hendy
- Brian Hood
- Chad A. Hamilton
- Christopher M. Tarney
- Clifton L Dalgard
- Coralie Viollet
- G. Larry Maxwell
- James Segars
- Julie Oliver
- Kathleen M Darcy
- Kelly Conrads
- Matthew Wilkerson
- Ming Zhou
- Nicholas W Bateman
- Paul Driggers
- Tamara Abulez
- Thomas P Conrads
- Tracy Litzi
- William H Catherino
- Yovanni Casablanca
Organizations
- Uniformed Services University of the Health Sciences