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

Lauren Brady, Michelle Kriner, Ilsa Coleman, Colm Morrissey, Martine Roudier, Lawrence D. True, Roman Gulati, Stephen R. Plymate, Zoey Zhou, Brian Birditt, Rhonda Meredith, Gary Geiss, Margaret Hoang, Joseph Beechem and Peter S. Nelson ()
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Lauren Brady: Fred Hutchinson Cancer Research Center
Michelle Kriner: NanoString Technologies, Inc.
Ilsa Coleman: Fred Hutchinson Cancer Research Center
Colm Morrissey: University of Washington
Martine Roudier: University of Washington
Lawrence D. True: University of Washington
Roman Gulati: Fred Hutchinson Cancer Research Center
Stephen R. Plymate: University of Washington
Zoey Zhou: NanoString Technologies, Inc.
Brian Birditt: NanoString Technologies, Inc.
Rhonda Meredith: NanoString Technologies, Inc.
Gary Geiss: NanoString Technologies, Inc.
Margaret Hoang: NanoString Technologies, Inc.
Joseph Beechem: NanoString Technologies, Inc.
Peter S. Nelson: Fred Hutchinson Cancer Research Center

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: Abstract 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.

Date: 2021
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DOI: 10.1038/s41467-021-21615-4

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