Integrated proteogenomics uncovers ancestry-specific and shared molecular drivers in localized prostate cancer
Schafer, C. C.; Abulez, T. S.; Zhang, X.; Ho, K.-L.; Jiang, J.; Young, D.; Fox, J.; Conrads, K. A.; Hood, B. L.; Sukumar, G.; Nousome, D.; Raj-Kumar, P.-K.; Russo, M.; Shafi, A. A.; Su, X. A.; Dobi, A.; Ali, A.; Elsamanoudi, S.; Cullen, J.; Figg, W. D.; Petrovics, G.; Dalgard, C. L.; Wilkerson, M. D.; Bateman, N. W.; Conrads, T. P.; Sesterhenn, I. A.; APOLLO Research Network, ; Ellis, L.; Shriver, C. D.; Chesnut, G. T.; Tan, S.-H.
Show abstract
Our integrative proteogenomics (genome, proteome and phosphoproteome) of localized prostate cancer (PCa) in an equal-access Military Health System patient cohort (57 Black and 55 White) revealed significant ancestry-associated differences. Somatic and germline regulatory differences converged on androgen, metabolic, PI3K/AKT/mTOR, and DNA damage response (DDR) pathways, with ancestry-specific immune- and stromal-associated signals. Black patients displayed greater genomic variability, enhanced androgen response, fatty-acid metabolism, and epithelial-mesenchymal transition, while White patients showed prevalent DDRG alterations, activated oncogenic signaling (MYC, E2F, mTORC1), and cell cycle regulation. Phosphoproteomics highlighted distinct kinase activities and candidate druggable dependencies. Multiomics integration revealed three exploratory tumor subtypes whose distinct biological programs were reproducibly validated. Ancestry-associated eQTLs supported inherited regulation of the proteome independent of CNAs. Ancestry-specific CNA and protein panels improved progression risk prediction beyond PSA and pathology models. These findings provide a framework for ancestry-informed prognostic models and generate testable hypotheses for precision therapies to reduce outcome disparities.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Convergent alterations in the tumor microenvironment of MYC-driven human and murine prostate cancer 97%
- Role of Specialized mSWI/SNF Complexes in Prostate Cancer Lineage Plasticity 96%
- The genomic landscape of metastatic castration-resistant prostate cancers reveals multiple distinct genotypes with potential clinical impact 96%
Similar papers in this journal
- Cell states and neighborhoods in distinct clinical stages of primary and metastatic esophageal adenocarcinoma 96%
- Enhancer profiling identifies epigenetic markers of endocrine resistance and reveals therapeutic options for metastatic castration-resistant prostate cancer patients 96%
- Determination of permissive and restraining cancer-associated fibroblast (DeCAF) subtypes 95%
Similar papers in this journal
- Scalable Screening of Ternary-Code DNA methylation Dynamics Associated with Human Traits. 96%
- Cystatin C is glucocorticoid-responsive, directs recruitment of Trem2+ macrophages and predicts failure of cancer immunotherapy 95%
- Long-read sequencing of diagnosis and post-therapy medulloblastoma reveals complex rearrangement patterns and epigenetic signatures 94%
Similar papers in this journal
- Cell cycle alterations associate with a redistribution of mutation rates across chromosomal domains in human cancers 95%
- Differential chromatin accessibility and transcriptional dynamics define breast cancer subtypes and their lineages 95%
- UnitedMet harnesses RNA-metabolite covariation to impute metabolite levels in clinical samples 94%
Similar papers in this journal
- Cis-Regulatory Element Hijacking by Structural Variants Overshadows Higher-Order Topological Changes in Primary Prostate Cancer 96%
- EZH2 synergizes with BRD4-NUT to drive NUT carcinoma growth through silencing of key tumor suppressor genes 94%
- Prostate cancer risk stratification via non-destructive 3D pathology with annotation-free gland segmentation and analysis 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.