Molecular integrative clustering of Asian gastric cell lines revealed two distinct chemosensitivity clusters

• Published in: PloS one 2014-10, Vol.9 (10), p.e111146
• Main Authors: Choong, Meng Ling, Tan, Shan Ho, Tan, Tuan Zea, Manesh, Sravanthy, Ngo, Anna, Yong, Jacklyn W Y, Yang, Henry He, Lee, May Ann
• Format: Article
• Language: English
• Subjects: Abnormalities; Antineoplastic Agents - pharmacology; Asian Continental Ancestry Group; Bioinformatics; Biology; Biology and life sciences; Biotechnology; Cancer; Cancer therapies; Cell Line, Tumor; Chemotherapy; Cluster Analysis; Clustering; Clusters; Comparative analysis; Copy number; Cytogenetics; Deoxyribonucleic acid; DNA; DNA methylation; Encyclopedias; Enrichment; Gastric cancer; Gene expression; Gene set enrichment analysis; Genes; Genetic abnormalities; Genomes; Growth factors; Heterogeneity; Humans; Hybridization; Inhibitory Concentration 50; Kinases; Medicine and Health Sciences; Metastasis; Mitochondria; Mutation; Mutation - genetics; Oxidative phosphorylation; People and Places; Phosphorylation; Principal components analysis; Protein Kinases - genetics; Research and Analysis Methods; Science; Signal Transduction - drug effects; Signaling; Stomach cancer; Stomach Neoplasms - genetics; Stomach Neoplasms - pathology; Transcription; Tumor cell lines
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0111146

Cell lines recapitulate cancer heterogeneity without the presence of interfering tissue found in primary tumor. Their heterogeneous characteristics are reflected in their multiple genetic abnormalities and variable responsiveness to drug treatments. In order to understand the heterogeneity observed in Asian gastric cancers, we have performed array comparative genomic hybridization (aCGH) on 18 Asian gastric cell lines. Hierarchical clustering and single-sample Gene Set Enrichment Analysis were performed on the aCGH data together with public gene expression data of the same cell lines obtained from the Cancer Cell Line Encyclopedia. We found a large amount of genetic aberrations, with some cell lines having 13 fold more aberrations than others. Frequently mutated genes and cellular pathways are identified in these Asian gastric cell lines. The combined analyses of aCGH and expression data demonstrate correlation of gene copy number variations and expression profiles in human gastric cancer cells. The gastric cell lines can be grouped into 2 integrative clusters (ICs). Gastric cells in IC1 are enriched with gene associated with mitochondrial activities and oxidative phosphorylation while cells in IC2 are enriched with genes associated with cell signaling and transcription regulations. The two clusters of cell lines were shown to have distinct responsiveness towards several chemotherapeutics agents such as PI3 K and proteosome inhibitors. Our molecular integrative clustering provides insight into critical genes and pathways that may be responsible for the differences in survival in response to chemotherapy.