Single cell analysis of cribriform prostate cancer reveals cell intrinsic and tumor microenvironmental pathways of aggressive disease.
Hong Yuen WongQuanhu ShengAmanda B HesterbergSarah CroessmannBrenda L RiosKhem GiriJorgen JacksonAdam X MirandaEvan WatkinsKerry R SchafferMeredith DonahueElizabeth WinklerDavid F PensonJoseph A SmithS Duke HerrellAmy N LuckenbaughDaniel A BarocasYoung J KimDiana GravesGiovanna A GiannicoJeffrey C RathmellBen H ParkJennifer B GordetskyPaula J HurleyPublished in: Nature communications (2022)
Cribriform prostate cancer, found in both invasive cribriform carcinoma (ICC) and intraductal carcinoma (IDC), is an aggressive histological subtype that is associated with progression to lethal disease. To delineate the molecular and cellular underpinnings of ICC/IDC aggressiveness, this study examines paired ICC/IDC and benign prostate surgical samples by single-cell RNA-sequencing, TCR sequencing, and histology. ICC/IDC cancer cells express genes associated with metastasis and targets with potential for therapeutic intervention. Pathway analyses and ligand/receptor status model cellular interactions among ICC/IDC and the tumor microenvironment (TME) including JAG1/NOTCH. The ICC/IDC TME is hallmarked by increased angiogenesis and immunosuppressive fibroblasts (CTHRC1 + ASPN + FAP + ENG + ) along with fewer T cells, elevated T cell dysfunction, and increased C1QB + TREM2 + APOE + -M2 macrophages. These findings support that cancer cell intrinsic pathways and a complex immunosuppressive TME contribute to the aggressive phenotype of ICC/IDC. These data highlight potential therapeutic opportunities to restore immune signaling in patients with ICC/IDC that may afford better outcomes.
Keyphrases
- single cell
- prostate cancer
- rna seq
- radical prostatectomy
- high throughput
- randomized controlled trial
- stem cells
- cell proliferation
- type diabetes
- climate change
- machine learning
- adipose tissue
- cell therapy
- cognitive decline
- extracellular matrix
- vascular endothelial growth factor
- single molecule
- human health
- weight loss
- data analysis
- benign prostatic hyperplasia