Differential effect of surgical manipulation on gene expression in normal breast tissue and breast tumor tissue

Inge Søkilde Pedersen, Mads Thomassen, Qihua Tan, Torben A Kruse, Ole Thorlacius-Ussing, Jens Peter Garne , Henrik Bygum Krarup

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Abstract

BACKGROUND:
Gene expression profiles of normal and tumor tissue reflect both differences in biological processes taking place in vivo and differences in response to stress during surgery and sample handling. The effect of cold (room temperature) ischemia in the time interval between surgical removal of the specimen and freezing is described in a few studies. However, not much is known about the effect of warm (body temperature) ischemia during surgery.

METHODS:
Three women with primary operable breast cancer underwent in situ biopsies from normal breast and tumor tissue prior to radical mastectomy. Ex vivo biopsies from normal and tumor tissue were collected immediately after surgical excision. The putative effects on gene expression of malignancy (tumor versus normal), surgical manipulation (post- versus pre-surgical) and interaction between the two (differences in effect of surgical manipulation on tumor and normal samples) were investigated simultaneously by Generalized Estimating Equation (GEE) analysis in this self-matched study.

RESULTS:
Gene set enrichment analysis (GSEA) demonstrates a marked difference in effect of surgical manipulation on tumor compared to normal tissue. Interestingly, a large proportion of pathways affected by ischemia especially in tumor tissue are pathways considered to be specifically up regulated in tumor tissue compared to normal.

CONCLUSION:
The results of this study suggest that a large contribution to this differential expression originates from altered response to stress in tumor cells rather than merely representing in vivo differences. It is important to bear this in mind when using gene-expression analysis to deduce biological function, and when collecting material for gene expression profiling.
Original languageEnglish
Article number57
JournalMolecular Medicine
Volume24
Number of pages8
ISSN1076-1551
DOIs
Publication statusPublished - 16. Nov 2018

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Neoplasms
Gene Expression Profiling
Transcriptome
Freezing

Keywords

  • : Specimen handling, Ischemia, Gene expression, Cell cycle, Cancer
  • Ischemia
  • Cell cycle
  • Gene expression
  • Specimen handling
  • Cancer
  • Humans
  • Middle Aged
  • Transcriptome
  • Cold Ischemia
  • Breast/metabolism
  • Warm Ischemia
  • Female
  • Breast Neoplasms/genetics

Cite this

Pedersen, Inge Søkilde ; Thomassen, Mads ; Tan, Qihua ; Kruse, Torben A ; Thorlacius-Ussing, Ole ; Garne , Jens Peter ; Krarup, Henrik Bygum. / Differential effect of surgical manipulation on gene expression in normal breast tissue and breast tumor tissue. In: Molecular Medicine. 2018 ; Vol. 24.
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abstract = "BACKGROUND:Gene expression profiles of normal and tumor tissue reflect both differences in biological processes taking place in vivo and differences in response to stress during surgery and sample handling. The effect of cold (room temperature) ischemia in the time interval between surgical removal of the specimen and freezing is described in a few studies. However, not much is known about the effect of warm (body temperature) ischemia during surgery.METHODS:Three women with primary operable breast cancer underwent in situ biopsies from normal breast and tumor tissue prior to radical mastectomy. Ex vivo biopsies from normal and tumor tissue were collected immediately after surgical excision. The putative effects on gene expression of malignancy (tumor versus normal), surgical manipulation (post- versus pre-surgical) and interaction between the two (differences in effect of surgical manipulation on tumor and normal samples) were investigated simultaneously by Generalized Estimating Equation (GEE) analysis in this self-matched study.RESULTS:Gene set enrichment analysis (GSEA) demonstrates a marked difference in effect of surgical manipulation on tumor compared to normal tissue. Interestingly, a large proportion of pathways affected by ischemia especially in tumor tissue are pathways considered to be specifically up regulated in tumor tissue compared to normal.CONCLUSION:The results of this study suggest that a large contribution to this differential expression originates from altered response to stress in tumor cells rather than merely representing in vivo differences. It is important to bear this in mind when using gene-expression analysis to deduce biological function, and when collecting material for gene expression profiling.",
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Differential effect of surgical manipulation on gene expression in normal breast tissue and breast tumor tissue. / Pedersen, Inge Søkilde; Thomassen, Mads; Tan, Qihua; Kruse, Torben A; Thorlacius-Ussing, Ole; Garne , Jens Peter; Krarup, Henrik Bygum.

In: Molecular Medicine, Vol. 24, 57, 16.11.2018.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Differential effect of surgical manipulation on gene expression in normal breast tissue and breast tumor tissue

AU - Pedersen, Inge Søkilde

AU - Thomassen, Mads

AU - Tan, Qihua

AU - Kruse, Torben A

AU - Thorlacius-Ussing, Ole

AU - Garne , Jens Peter

AU - Krarup, Henrik Bygum

PY - 2018/11/16

Y1 - 2018/11/16

N2 - BACKGROUND:Gene expression profiles of normal and tumor tissue reflect both differences in biological processes taking place in vivo and differences in response to stress during surgery and sample handling. The effect of cold (room temperature) ischemia in the time interval between surgical removal of the specimen and freezing is described in a few studies. However, not much is known about the effect of warm (body temperature) ischemia during surgery.METHODS:Three women with primary operable breast cancer underwent in situ biopsies from normal breast and tumor tissue prior to radical mastectomy. Ex vivo biopsies from normal and tumor tissue were collected immediately after surgical excision. The putative effects on gene expression of malignancy (tumor versus normal), surgical manipulation (post- versus pre-surgical) and interaction between the two (differences in effect of surgical manipulation on tumor and normal samples) were investigated simultaneously by Generalized Estimating Equation (GEE) analysis in this self-matched study.RESULTS:Gene set enrichment analysis (GSEA) demonstrates a marked difference in effect of surgical manipulation on tumor compared to normal tissue. Interestingly, a large proportion of pathways affected by ischemia especially in tumor tissue are pathways considered to be specifically up regulated in tumor tissue compared to normal.CONCLUSION:The results of this study suggest that a large contribution to this differential expression originates from altered response to stress in tumor cells rather than merely representing in vivo differences. It is important to bear this in mind when using gene-expression analysis to deduce biological function, and when collecting material for gene expression profiling.

AB - BACKGROUND:Gene expression profiles of normal and tumor tissue reflect both differences in biological processes taking place in vivo and differences in response to stress during surgery and sample handling. The effect of cold (room temperature) ischemia in the time interval between surgical removal of the specimen and freezing is described in a few studies. However, not much is known about the effect of warm (body temperature) ischemia during surgery.METHODS:Three women with primary operable breast cancer underwent in situ biopsies from normal breast and tumor tissue prior to radical mastectomy. Ex vivo biopsies from normal and tumor tissue were collected immediately after surgical excision. The putative effects on gene expression of malignancy (tumor versus normal), surgical manipulation (post- versus pre-surgical) and interaction between the two (differences in effect of surgical manipulation on tumor and normal samples) were investigated simultaneously by Generalized Estimating Equation (GEE) analysis in this self-matched study.RESULTS:Gene set enrichment analysis (GSEA) demonstrates a marked difference in effect of surgical manipulation on tumor compared to normal tissue. Interestingly, a large proportion of pathways affected by ischemia especially in tumor tissue are pathways considered to be specifically up regulated in tumor tissue compared to normal.CONCLUSION:The results of this study suggest that a large contribution to this differential expression originates from altered response to stress in tumor cells rather than merely representing in vivo differences. It is important to bear this in mind when using gene-expression analysis to deduce biological function, and when collecting material for gene expression profiling.

KW - : Specimen handling, Ischemia, Gene expression, Cell cycle, Cancer

KW - Ischemia

KW - Cell cycle

KW - Gene expression

KW - Specimen handling

KW - Cancer

KW - Humans

KW - Middle Aged

KW - Transcriptome

KW - Cold Ischemia

KW - Breast/metabolism

KW - Warm Ischemia

KW - Female

KW - Breast Neoplasms/genetics

U2 - 10.1186/s10020-018-0058-x

DO - 10.1186/s10020-018-0058-x

M3 - Journal article

VL - 24

JO - Molecular Medicine

JF - Molecular Medicine

SN - 1076-1551

M1 - 57

ER -