Patient-matched analysis identifies deregulated networks in prostate cancer to guide personalized therapeutic intervention
Kumar, A.; Badredine, A.; Azzag, K.; Kasikci, Y.; Ranty, M. L. Q.; Zaidi, F.; Serret, N.; Mazerolles, C.; Malavaud, B.; Mendoza-Parra, M. A.; Vandel, L.; Gronemeyer, H.
Show abstract
Prostate cancer (PrCa) is the second most common malignancy in men1. More than 50% of advanced prostate cancers display the TMPRSS2-ERG fusion2. Despite extensive cancer genome/transcriptome2-4 and phosphoproteome5 data, little is known about the impact of mutations and altered transcription on regulatory networks in the PrCa of individual patients. Using patient-matched normal and tumor samples, we established somatic variations and differential transcriptome profiles of primary ERG-positive prostate cancers. Integration of protein-protein interaction and gene-regulatory network databases6, 7 defined highly diverse patient-specific network alterations. We found that different components of a given regulatory pathway were altered by novel and known mutations and/or aberrant gene expression, including deregulated ERG targets, such that different sets of pathways were altered in each individual PrCa. In a given PrCa, several deregulated pathways share common factors, predicting synergistic effects on cancer progression. Our integrated analysis provides a paradigm to identify key deregulated factors within regulatory networks to guide personalized therapies.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
Similar papers in this journal
- Global loss of promoter-enhancer connectivity and rebalancing of gene expression during early colorectal cancer carcinogenesis 96%
- Cell cycle alterations associate with a redistribution of mutation rates across chromosomal domains in human cancers 96%
- Differential chromatin accessibility and transcriptional dynamics define breast cancer subtypes and their lineages 96%
Similar papers in this journal
- Normal and cancer tissues are accurately characterised by intergenic transcription at RNA polymerase 2 binding sites 96%
- Implications of noncoding regulatory functions in the development of insulinomas 95%
- Long-read sequencing of diagnosis and post-therapy medulloblastoma reveals complex rearrangement patterns and epigenetic signatures 95%
"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.