Inter- and Intra-tumor Heterogeneity of Metastatic Prostate Cancer Determined by Digital Spatial Gene Expression Profiling

Overview

Journal Nat Commun

Specialty Biology

Date 2021 Mar 4

PMID 33658518

Citations 119

Authors

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

Peter S Nelson

Affiliations

Soon will be listed here.

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.

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