Convergent genomic and molecular features predict risk of metachronous metastasis in clear cell renal cell carcinoma
Naeini, M. M.; Pang, M.; Rohatgi, N.; Kadioglu, S.; Ghoshdastider, U.; DiNatale, R. G.; Mano, R.; Hakimi, A. A.; Skanderup, A. J.
Show abstract
The molecular features determining the risk of metachronous metastases in clear cell renal cell carcinoma (ccRCC) are poorly defined. Using a systematic tumor transcriptome deconvolution approach, we investigated the genomic and transcriptomic profiles of 192 ccRCC primary tumors with extended clinical follow-up to identify cancer and stromal cell molecular features associated with metastatic risk. At the genomic level, we identified a significantly higher frequency of copy number loss at 1p31-36 in primary tumors that later progressed with metastases. Tumor transcriptome deconvolution identified significant down-regulation of epithelial cell polarity, including PATJ (1p31), and fatty acid metabolism, including CYP4A11 (1p33), in cancer cells of tumors that developed metastatic progression. We developed and benchmarked a compact 5-feature predictive model (5G) that demonstrated improved accuracy over existing ccRCC gene signatures in the prediction of metachronous metastasis risk. Overall, our study highlights convergent genomic and transcriptomic alterations in chromosome 1p, driving dysregulation of epithelial cell polarity and fatty acid metabolism, as putative novel risk factors of metachronous metastasis in ccRCC.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- Distinct cell adhesion signature defines glioblastoma myeloid-derived suppressor cell subsets 93%
- Long-term ovarian cancer survivors: spatial transcriptomics depict ligand-receptor crosstalk heterogeneity at the tumor-stroma interface 93%
- Spatiotemporal profiling defines persistence and resistance dynamics during targeted treatment of melanoma 93%
Similar papers in this journal
- Evolutionary states and trajectories characterized by distinct pathways stratify ovarian high-grade serous carcinoma patients 95%
- Clinical and molecular features of acquired resistance to immunotherapy in non-small cell lung cancer 94%
- Coexisting morpho-biotypes unveil the regulatory bases of phenotypic plasticity in pancreatic ductal adenocarcinoma 94%
Similar papers in this journal
- Genome profiles of lymphovascular breast cancer cells reveal multiple clonally differentiated outcomes with multi-regional LCM and G&T-seq 93%
- Determination of permissive and restraining cancer-associated fibroblast (DeCAF) subtypes 93%
- Coordinated macrophage and T cell interactions mediate response to checkpoint blockade in colorectal cancer. 92%
"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.