Inter- and intra-tumor heterogeneity of metastatic prostate cancer determined by digital spatial gene expression profiling

Nat Commun. 2021 Mar 3;12(1):1426. doi: 10.1038/s41467-021-21615-4.


Metastatic prostate cancer (mPC) comprises a spectrum of diverse phenotypes. However, the extent of inter- and intra-tumor heterogeneity is not established. Here we use digital spatial profiling (DSP) technology to quantitate transcript and protein abundance in spatially-distinct regions of mPCs. By assessing multiple discrete areas across multiple metastases, we find a high level of intra-patient homogeneity with respect to tumor phenotype. However, there are notable exceptions including tumors comprised of regions with high and low androgen receptor (AR) and neuroendocrine activity. While the vast majority of metastases examined are devoid of significant inflammatory infiltrates and lack PD1, PD-L1 and CTLA4, the B7-H3/CD276 immune checkpoint protein is highly expressed, particularly in mPCs with high AR activity. Our results demonstrate the utility of DSP for accurately classifying tumor phenotype, assessing tumor heterogeneity, and identifying aspects of tumor biology involving the immunological composition of metastases.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • B7 Antigens / genetics
  • B7-H1 Antigen / genetics
  • CTLA-4 Antigen / genetics
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Neoplastic
  • Hepatitis A Virus Cellular Receptor 2 / genetics
  • Humans
  • Male
  • Paraffin Embedding
  • Phenotype
  • Programmed Cell Death 1 Receptor / genetics
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology*
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism
  • Tissue Array Analysis
  • Transcriptome


  • AR protein, human
  • B7 Antigens
  • B7-H1 Antigen
  • CD274 protein, human
  • CD276 protein, human
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • HAVCR2 protein, human
  • Hepatitis A Virus Cellular Receptor 2
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Receptors, Androgen