Identification of novel oncogenic events occurring early in prostate carcinogenesis using purified autologous malignant and non-malignant prostate epithelial cells

Pavel Sluka, Carmel Pezaro, Hady Wardan, Shomik Sengupta, I. D. Davis

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Objective: To interrogate enriched prostate cancer cells and autologous non-malignant prostate epithelial cells from men with localized prostate cancer, in order to identify early oncogenic pathways. Patients and Methods: We collected malignant and matched non-malignant prostatectomy samples from men with adenocarcinoma involving two or more contiguous areas in only one lobe of the prostate. Tissue samples from both lobes were subjected to digestion and single-cell suspensions were prepared. Epithelial cell adhesion molecule-positive cells from cancerous and contralateral non-malignant (control) samples were isolated using magnetic beads, ensuring uniform populations were obtained for each donor. Unbiased RNA sequencing analysis was used to measure gene expression and for detection of transcribed mutations or splice variants that were over- or under-represented in malignant prostate epithelial cells relative to autologous control prostate epithelial cells. Results: From five patient samples we identified 17 genes that were altered in prostate cancer epithelial cells, with 82% of genes being downregulated. Three genes, TDRD1, ANGTL4, and CLDN3, were consistently upregulated in malignant tissue. Malignant cells from three of the five patients showed evidence of upregulated ERG signalling, however, only one of these contained a TMPRSS2-ERG rearrangement. We did not identify mutations, gene rearrangements, or splice variants that were consistent amongst the patients. Conclusions: Events occurring early in prostate cancer oncogenesis in these samples were characterized by a predominant downregulation of gene expression along with upregulation of TDRD1, ANGTL4 and CLDN3. No consistent mutations or splice variants were observed, but upregulation of ERG signalling was seen both in the presence and absence of the classic TMPRSS2-ERG rearrangement.

Original languageEnglish
Pages (from-to)27-35
Number of pages9
JournalBJU International
Volume123
Issue numberS5
DOIs
Publication statusPublished - 1 May 2019

Keywords

  • #PCSM
  • #ProstateCancer
  • carcinogenesis
  • gene rearrangement
  • prostate cancer

Cite this

@article{1ffa9be7dd6b4e6291a1315f8c23c6a7,
title = "Identification of novel oncogenic events occurring early in prostate carcinogenesis using purified autologous malignant and non-malignant prostate epithelial cells",
abstract = "Objective: To interrogate enriched prostate cancer cells and autologous non-malignant prostate epithelial cells from men with localized prostate cancer, in order to identify early oncogenic pathways. Patients and Methods: We collected malignant and matched non-malignant prostatectomy samples from men with adenocarcinoma involving two or more contiguous areas in only one lobe of the prostate. Tissue samples from both lobes were subjected to digestion and single-cell suspensions were prepared. Epithelial cell adhesion molecule-positive cells from cancerous and contralateral non-malignant (control) samples were isolated using magnetic beads, ensuring uniform populations were obtained for each donor. Unbiased RNA sequencing analysis was used to measure gene expression and for detection of transcribed mutations or splice variants that were over- or under-represented in malignant prostate epithelial cells relative to autologous control prostate epithelial cells. Results: From five patient samples we identified 17 genes that were altered in prostate cancer epithelial cells, with 82{\%} of genes being downregulated. Three genes, TDRD1, ANGTL4, and CLDN3, were consistently upregulated in malignant tissue. Malignant cells from three of the five patients showed evidence of upregulated ERG signalling, however, only one of these contained a TMPRSS2-ERG rearrangement. We did not identify mutations, gene rearrangements, or splice variants that were consistent amongst the patients. Conclusions: Events occurring early in prostate cancer oncogenesis in these samples were characterized by a predominant downregulation of gene expression along with upregulation of TDRD1, ANGTL4 and CLDN3. No consistent mutations or splice variants were observed, but upregulation of ERG signalling was seen both in the presence and absence of the classic TMPRSS2-ERG rearrangement.",
keywords = "#PCSM, #ProstateCancer, carcinogenesis, gene rearrangement, prostate cancer",
author = "Pavel Sluka and Carmel Pezaro and Hady Wardan and Shomik Sengupta and Davis, {I. D.}",
note = "1464-410x Sluka, Pavel Pezaro, Carmel Wardan, Hady Sengupta, Shomik Davis, Ian D Journal Article England BJU Int. 2019 Feb 3. doi: 10.1111/bju.14695.",
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Identification of novel oncogenic events occurring early in prostate carcinogenesis using purified autologous malignant and non-malignant prostate epithelial cells. / Sluka, Pavel; Pezaro, Carmel; Wardan, Hady; Sengupta, Shomik; Davis, I. D.

In: BJU International, Vol. 123, No. S5, 01.05.2019, p. 27-35.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Identification of novel oncogenic events occurring early in prostate carcinogenesis using purified autologous malignant and non-malignant prostate epithelial cells

AU - Sluka, Pavel

AU - Pezaro, Carmel

AU - Wardan, Hady

AU - Sengupta, Shomik

AU - Davis, I. D.

N1 - 1464-410x Sluka, Pavel Pezaro, Carmel Wardan, Hady Sengupta, Shomik Davis, Ian D Journal Article England BJU Int. 2019 Feb 3. doi: 10.1111/bju.14695.

PY - 2019/5/1

Y1 - 2019/5/1

N2 - Objective: To interrogate enriched prostate cancer cells and autologous non-malignant prostate epithelial cells from men with localized prostate cancer, in order to identify early oncogenic pathways. Patients and Methods: We collected malignant and matched non-malignant prostatectomy samples from men with adenocarcinoma involving two or more contiguous areas in only one lobe of the prostate. Tissue samples from both lobes were subjected to digestion and single-cell suspensions were prepared. Epithelial cell adhesion molecule-positive cells from cancerous and contralateral non-malignant (control) samples were isolated using magnetic beads, ensuring uniform populations were obtained for each donor. Unbiased RNA sequencing analysis was used to measure gene expression and for detection of transcribed mutations or splice variants that were over- or under-represented in malignant prostate epithelial cells relative to autologous control prostate epithelial cells. Results: From five patient samples we identified 17 genes that were altered in prostate cancer epithelial cells, with 82% of genes being downregulated. Three genes, TDRD1, ANGTL4, and CLDN3, were consistently upregulated in malignant tissue. Malignant cells from three of the five patients showed evidence of upregulated ERG signalling, however, only one of these contained a TMPRSS2-ERG rearrangement. We did not identify mutations, gene rearrangements, or splice variants that were consistent amongst the patients. Conclusions: Events occurring early in prostate cancer oncogenesis in these samples were characterized by a predominant downregulation of gene expression along with upregulation of TDRD1, ANGTL4 and CLDN3. No consistent mutations or splice variants were observed, but upregulation of ERG signalling was seen both in the presence and absence of the classic TMPRSS2-ERG rearrangement.

AB - Objective: To interrogate enriched prostate cancer cells and autologous non-malignant prostate epithelial cells from men with localized prostate cancer, in order to identify early oncogenic pathways. Patients and Methods: We collected malignant and matched non-malignant prostatectomy samples from men with adenocarcinoma involving two or more contiguous areas in only one lobe of the prostate. Tissue samples from both lobes were subjected to digestion and single-cell suspensions were prepared. Epithelial cell adhesion molecule-positive cells from cancerous and contralateral non-malignant (control) samples were isolated using magnetic beads, ensuring uniform populations were obtained for each donor. Unbiased RNA sequencing analysis was used to measure gene expression and for detection of transcribed mutations or splice variants that were over- or under-represented in malignant prostate epithelial cells relative to autologous control prostate epithelial cells. Results: From five patient samples we identified 17 genes that were altered in prostate cancer epithelial cells, with 82% of genes being downregulated. Three genes, TDRD1, ANGTL4, and CLDN3, were consistently upregulated in malignant tissue. Malignant cells from three of the five patients showed evidence of upregulated ERG signalling, however, only one of these contained a TMPRSS2-ERG rearrangement. We did not identify mutations, gene rearrangements, or splice variants that were consistent amongst the patients. Conclusions: Events occurring early in prostate cancer oncogenesis in these samples were characterized by a predominant downregulation of gene expression along with upregulation of TDRD1, ANGTL4 and CLDN3. No consistent mutations or splice variants were observed, but upregulation of ERG signalling was seen both in the presence and absence of the classic TMPRSS2-ERG rearrangement.

KW - #PCSM

KW - #ProstateCancer

KW - carcinogenesis

KW - gene rearrangement

KW - prostate cancer

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U2 - 10.1111/bju.14695

DO - 10.1111/bju.14695

M3 - Article

VL - 123

SP - 27

EP - 35

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JF - BJU International

SN - 1464-4096

IS - S5

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