Meta-Analysis of Tumor Stem-Like Breast Cancer Cells Using Gene Set and Network Analysis

• Published in: PloS one Vol. 11; no. 2; p. e0148818
• Main Authors: Lee, Won Jun, Kim, Sang Cheol, Yoon, Jung-Ho, Yoon, Sang Jun, Lim, Johan, Kim, You-Sun, Kwon, Sung Won, Park, Jeong Hill
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 12.02.2016; Public Library of Science (PLoS)
• Subjects: Addition polymerization; Biochemistry; Biology and Life Sciences; Biomarkers; Breast cancer; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer; Cancer cells; Cancer therapies; Cell adhesion & migration; Cell Line, Tumor; Comparative analysis; CXCR4 protein; Data collection; Datasets; Development and progression; Epithelial-Mesenchymal Transition; Female; Gene expression; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Genes; Genetic aspects; Genomes; Humans; Identification methods; Medical research; Medicine and Health Sciences; Mesenchyme; Meta-analysis; Metastases; Metastasis; Neoplastic Stem Cells - metabolism; Network analysis; Pancreatic cancer; Pharmaceutical sciences; Pharmacy; Physical Sciences; Physiological aspects; Polymerase chain reaction; Research and Analysis Methods; Reverse transcription; Stem cells; Studies; Transcriptome; Tumors; South Korea
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0148818

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 up-regulation 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.