Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Dec 15;153(12):2055-2067.
doi: 10.1002/ijc.34708. Epub 2023 Sep 1.

Spatial whole transcriptome profiling of primary tumor from patients with metastatic prostate cancer

Paul Vinu Salachan  1   2 , Martin Rasmussen  1   2 , Benedicte Parm Ulhøi  3 , Jørgen Bjerggaard Jensen  2   4 , Michael Borre  2   5 , Karina Dalsgaard Sørensen  1   2
Affiliations

Spatial whole transcriptome profiling of primary tumor from patients with metastatic prostate cancer

Paul Vinu Salachan et al. Int J Cancer. .

Abstract

Prostate cancer (PCa) is a highly heterogeneous disease in terms of its molecular makeup and clinical prognosis. The prostate tumor microenvironment (TME) is hypothesized to play an important role in driving disease aggressiveness, but precise mechanisms remain elusive. In our study, we used spatial transcriptomics to explore for the first time the spatial gene expression heterogeneity within primary prostate tumors from patients with metastatic disease. In total, we analyzed 5459 tissue spots from three PCa patients comprising castration-resistant (CRPC) and neuroendocrine (NEPC) disease stages. Within CRPC, we identified a T cell cluster whose activity might be impaired by nearby regulatory T cells, potentially mediating the aggressive disease phenotype. Moreover, we identified Hallmark signatures of epithelial-mesenchymal transition in a cancer-associated fibroblast (CAF) cluster, indicating the aggressive characteristic of the primary TME leading to metastatic dissemination. Within NEPC, we identified active immune-stroma cross-talk exemplified by significant ligand-receptor interactions between CAFs and M2 macrophages. Further, we identified a malignant cell population that was associated with the down-regulation of an immune-related gene signature. Lower expression of this signature was associated with higher levels of genomic instability in advanced PCa patients (SU2C cohort, n = 99) and poor recurrence free survival in early-stage PCa patients (TCGA cohort, n = 395), suggesting prognostic biomarker potential. Taken together, our study reveals the importance of whole transcriptome profiling at spatial resolution for biomarker discovery and for advancing our understanding of tumor biology.

Keywords: cancer-associated fibroblasts; immune checkpoint targets; metastatic prostate cancer; spatial gene expression; tumor microenvironment.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

REFERENCES

    1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209-249. doi:10.3322/caac.21660
    1. Lu-Yao GL, Potosky AL, Albertsen PC, Wasson JH, Barry MJ, Wennberg JE. Follow-up prostate cancer treatments after radical prostatectomy: a population-based study. J Natl Cancer Inst. 1996;88(3-4):166-173. doi:10.1093/jnci/88.3-4.166
    1. Farach A, Ding Y, Lee M, et al. Neuronal trans-differentiation in prostate cancer cells. Prostate. 2016;76(14):1312-1325. doi:10.1002/pros.23221
    1. Andersen LB, Norgaard M, Rasmussen M, et al. Immune cell analyses of the tumor microenvironment in prostate cancer highlight infiltrating regulatory T cells and macrophages as adverse prognostic factors. J Pathol. 2021;255:155-165. doi:10.1002/path.5757
    1. R core Team. R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing. Vienna, Austria; 2020.

Publication types

LinkOut - more resources