A gene expression signature that defines breast cancer metastases (2023)

Ellsworth, R. E., Seebach, J., Field, L. A., Heckman, C., Kane, J., Hooke, J. A., Love, B. (2009). A gene expression signature that defines breast cancer metastases. Clinical and Experimental Metastasis, 26(3), 205-213. https://doi.org/10.1007/s10585-008-9232-9

Ellsworth, Rachel E. ; Seebach, Jeff ; Field, Lori A. et al. / A gene expression signature that defines breast cancer metastases. In: Clinical and Experimental Metastasis. 2009 ; Vol. 26, No. 3. pp. 205-213.

@article{692f5399d30b4930b05bf7be9a4677d5,

title = "A gene expression signature that defines breast cancer metastases",

abstract = "The most important predictor of prognosis in breast cancer is lymph node status, yet little is known about molecular changes associated with lymph node metastasis. Here, gene expression analysis was performed on primary breast (PBT) and corresponding metastatic lymph node (MLN) tumors to identify molecular signatures associated with nodal metastasis. RNA was isolated after laser microdissection from frozen PBT and MLN from 20 patients with positive lymph nodes and hybridized to the microarray chips. Differential expression was determined using Mann-Whitney testing; Bonferroni corrected P values of 0.05 and 0.001 were calculated. Results were validated using TaqMan assays. Fifty-one genes were differentially expressed (P < 1 × 10-5, less than twofold differences) between the PBT and paired MLN; 13 with significantly higher expression in the MLN and 38 in the PBT. qRT-PCR validated the differential expression of 40/51 genes. Of the 40 validated genes, NTS and PAX5 were found to have >100-fold higher expression in MLT while COL11A1, KRT14, MMP13, TAC1 and WNT2 had >100-fold higher expression in PBT. Gene expression differences between PBT and MLN suggests that expression of a unique set of genes is required for successful lymph node colonization. Genes expressed at higher levels in PBT are involved in degradation of the extracellular matrix, enabling cells with metastatic potential to disseminate, while genes expressed at higher levels in metastases are involved in transcription, signal transduction and immune response, providing cells with proliferation and survival advantages. These data improve our understanding of the biological processes involved in successful metastatis and provide new targets to arrest tumor cell dissemination and metastatic colonization.",

keywords = "Breast cancer, Gene expression, Metastasis",

author = "Ellsworth, {Rachel E.} and Jeff Seebach and Field, {Lori A.} and Caroline Heckman and Jennifer Kane and Hooke, {Jeffrey A.} and Brad Love and Shriver, {Craig D.}",

note = "Funding Information: Acknowledgments We thank Drs. Darrell Ellsworth and George Iida for helpful and critical review of this manuscript. Supported by the United States Department of Defense (Military Molecular Medicine Initiative MDA W81XWH-05-2-0075). The opinion and assertions contained herein are the private views of the authors and are not to be construed as official or as representing the views of the Department of the Army or the Department of Defense.",

year = "2009",

month = mar,

doi = "10.1007/s10585-008-9232-9",

language = "English",

volume = "26",

pages = "205--213",

journal = "Clinical and Experimental Metastasis",

issn = "0262-0898",

number = "3",

}

Ellsworth, RE, Seebach, J, Field, LA, Heckman, C, Kane, J, Hooke, JA, Love, B 2009, 'A gene expression signature that defines breast cancer metastases', Clinical and Experimental Metastasis, vol. 26, no. 3, pp. 205-213. https://doi.org/10.1007/s10585-008-9232-9

A gene expression signature that defines breast cancer metastases. / Ellsworth, Rachel E.; Seebach, Jeff; Field, Lori A. et al.

In: Clinical and Experimental Metastasis, Vol. 26, No. 3, 03.2009, p. 205-213.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - A gene expression signature that defines breast cancer metastases

AU - Ellsworth, Rachel E.

AU - Seebach, Jeff

AU - Field, Lori A.

AU - Heckman, Caroline

AU - Kane, Jennifer

AU - Hooke, Jeffrey A.

AU - Love, Brad

AU - Shriver, Craig D.

N1 - Funding Information:Acknowledgments We thank Drs. Darrell Ellsworth and George Iida for helpful and critical review of this manuscript. Supported by the United States Department of Defense (Military Molecular Medicine Initiative MDA W81XWH-05-2-0075). The opinion and assertions contained herein are the private views of the authors and are not to be construed as official or as representing the views of the Department of the Army or the Department of Defense.

PY - 2009/3

Y1 - 2009/3

N2 - The most important predictor of prognosis in breast cancer is lymph node status, yet little is known about molecular changes associated with lymph node metastasis. Here, gene expression analysis was performed on primary breast (PBT) and corresponding metastatic lymph node (MLN) tumors to identify molecular signatures associated with nodal metastasis. RNA was isolated after laser microdissection from frozen PBT and MLN from 20 patients with positive lymph nodes and hybridized to the microarray chips. Differential expression was determined using Mann-Whitney testing; Bonferroni corrected P values of 0.05 and 0.001 were calculated. Results were validated using TaqMan assays. Fifty-one genes were differentially expressed (P < 1 × 10-5, less than twofold differences) between the PBT and paired MLN; 13 with significantly higher expression in the MLN and 38 in the PBT. qRT-PCR validated the differential expression of 40/51 genes. Of the 40 validated genes, NTS and PAX5 were found to have >100-fold higher expression in MLT while COL11A1, KRT14, MMP13, TAC1 and WNT2 had >100-fold higher expression in PBT. Gene expression differences between PBT and MLN suggests that expression of a unique set of genes is required for successful lymph node colonization. Genes expressed at higher levels in PBT are involved in degradation of the extracellular matrix, enabling cells with metastatic potential to disseminate, while genes expressed at higher levels in metastases are involved in transcription, signal transduction and immune response, providing cells with proliferation and survival advantages. These data improve our understanding of the biological processes involved in successful metastatis and provide new targets to arrest tumor cell dissemination and metastatic colonization.

AB - The most important predictor of prognosis in breast cancer is lymph node status, yet little is known about molecular changes associated with lymph node metastasis. Here, gene expression analysis was performed on primary breast (PBT) and corresponding metastatic lymph node (MLN) tumors to identify molecular signatures associated with nodal metastasis. RNA was isolated after laser microdissection from frozen PBT and MLN from 20 patients with positive lymph nodes and hybridized to the microarray chips. Differential expression was determined using Mann-Whitney testing; Bonferroni corrected P values of 0.05 and 0.001 were calculated. Results were validated using TaqMan assays. Fifty-one genes were differentially expressed (P < 1 × 10-5, less than twofold differences) between the PBT and paired MLN; 13 with significantly higher expression in the MLN and 38 in the PBT. qRT-PCR validated the differential expression of 40/51 genes. Of the 40 validated genes, NTS and PAX5 were found to have >100-fold higher expression in MLT while COL11A1, KRT14, MMP13, TAC1 and WNT2 had >100-fold higher expression in PBT. Gene expression differences between PBT and MLN suggests that expression of a unique set of genes is required for successful lymph node colonization. Genes expressed at higher levels in PBT are involved in degradation of the extracellular matrix, enabling cells with metastatic potential to disseminate, while genes expressed at higher levels in metastases are involved in transcription, signal transduction and immune response, providing cells with proliferation and survival advantages. These data improve our understanding of the biological processes involved in successful metastatis and provide new targets to arrest tumor cell dissemination and metastatic colonization.

KW - Breast cancer

KW - Gene expression

KW - Metastasis

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U2 - 10.1007/s10585-008-9232-9

DO - 10.1007/s10585-008-9232-9

M3 - Article

C2 - 19112599

AN - SCOPUS:61449137705

VL - 26

SP - 205

EP - 213

JO - Clinical and Experimental Metastasis

JF - Clinical and Experimental Metastasis

SN - 0262-0898

IS - 3

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Ellsworth RE, Seebach J, Field LA, Heckman C, Kane J, Hooke JA et al. A gene expression signature that defines breast cancer metastases. Clinical and Experimental Metastasis. 2009 Mar;26(3):205-213. https://doi.org/10.1007/s10585-008-9232-9