Meta-analysis of tumor stem-like breast cancer cells using gene set and network analysis

Won Jun Lee, Sang Cheol Kim, Jung Ho Yoon, Sang Jun Yoon, Johan Lim, You Sun Kim, Sung Won Kwon, Jeong Hill Park

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Generally, cancer stem cells have epithelial-to-mesenchymal-transition characteristics and other aggressive properties that cause metastasis. However, there have been no confident markers for the identification of cancer stem cells and comparative methods examining adherent and sphere cells are widely used to investigate mechanism underlying cancer stem cells, because sphere cells have been known to maintain cancer stem cell characteristics. In this study, we conducted a meta-analysis that combined gene expression profiles from several studies that utilized tumorsphere technology to investigate tumor stem-like breast cancer cells. We used our own gene expression profiles along with the three different gene expression profiles from the Gene Expression Omnibus, which we combined using the ComBat method, and obtained significant gene sets using the gene set analysis of our datasets and the combined dataset. This experiment focused on four gene sets such as cytokine-cytokine receptor interaction that demonstrated significance in both datasets. Our observations demonstrated that among the genes of four significant gene sets, six genes were consistently up-regulated and satisfied the p-value of <0.05, and our network analysis showed high connectivity in five genes. From these results, we established CXCR4, CXCL1 and HMGCS1, the intersecting genes of the datasets with high connectivity and p-value of <0.05, as significant genes in the identification of cancer stem cells. Additional experiment using quantitative reverse transcription-polymerase chain reaction showed significant upregulation in MCF-7 derived sphere cells and confirmed the importance of these three genes. Taken together, using meta-analysis that combines gene set and network analysis, we suggested CXCR4, CXCL1 and HMGCS1 as candidates involved in tumor stem-like breast cancer cells. Distinct from other meta-analysis, by using gene set analysis, we selected possible markers which can explain the biological mechanisms and suggested network analysis as an additional criterion for selecting candidates.

Original languageEnglish (US)
Article numbere0148818
JournalPLoS One
Volume11
Issue number2
DOIs
StatePublished - Feb 1 2016

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Gene Regulatory Networks
Electric network analysis
meta-analysis
breast neoplasms
Meta-Analysis
Tumors
Genes
Cells
Breast Neoplasms
neoplasms
stems
Neoplastic Stem Cells
Stem cells
Neoplasms
genes
stem cells
Gene expression
Transcriptome
gene expression
neoplasm cells

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Lee, W. J., Kim, S. C., Yoon, J. H., Yoon, S. J., Lim, J., Kim, Y. S., ... Park, J. H. (2016). Meta-analysis of tumor stem-like breast cancer cells using gene set and network analysis. PLoS One, 11(2), [e0148818]. https://doi.org/10.1371/journal.pone.0148818

Meta-analysis of tumor stem-like breast cancer cells using gene set and network analysis. / Lee, Won Jun; Kim, Sang Cheol; Yoon, Jung Ho; Yoon, Sang Jun; Lim, Johan; Kim, You Sun; Kwon, Sung Won; Park, Jeong Hill.

In: PLoS One, Vol. 11, No. 2, e0148818, 01.02.2016.

Research output: Contribution to journalArticle

Lee, WJ, Kim, SC, Yoon, JH, Yoon, SJ, Lim, J, Kim, YS, Kwon, SW & Park, JH 2016, 'Meta-analysis of tumor stem-like breast cancer cells using gene set and network analysis', PLoS One, vol. 11, no. 2, e0148818. https://doi.org/10.1371/journal.pone.0148818
Lee, Won Jun ; Kim, Sang Cheol ; Yoon, Jung Ho ; Yoon, Sang Jun ; Lim, Johan ; Kim, You Sun ; Kwon, Sung Won ; Park, Jeong Hill. / Meta-analysis of tumor stem-like breast cancer cells using gene set and network analysis. In: PLoS One. 2016 ; Vol. 11, No. 2.
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