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Expression genomics in breast cancer research: microarrays at the crossroads of biology and medicine.

ABSTRACT: Genome-wide expression microarray studies have revealed that the biological and clinical heterogeneity of breast cancer can be partly explained by information embedded within a complex but ordered transcriptional architecture. Comprising this architecture are gene expression networks, or signatures, reflecting biochemical and behavioral properties of tumors that might be harnessed to improve disease subtyping, patient prognosis and prediction of therapeutic response. Emerging 'hypothesis-driven' strategies that incorporate knowledge of pathways and other biological phenomena in the signature discovery process are linking prognosis and therapy prediction with transcriptional readouts of tumorigenic mechanisms that better inform therapeutic options.

SUBMITTER: Miller LD

PROVIDER: S-EPMC1868923 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundOvarian cancer is one of the rarest lethal oncologic diseases that have hardly any specific biomarkers. The availability of high-throughput genomic data and advancement in bioinformatics tools allow us to predict gene biomarkers and apply systems biology approaches to get better diagnosis, and prognosis of the disease with a tentative drug that may be repurposed.ObjectiveTo perform genome-wide association studies using microarray gene expression of ovarian cancer and identify gene biomarkers, construction and analyze networks, perform survival analysis, and drug interaction studies for better diagnosis, prognosis, and treatment of ovarian cancer.MethodThe gene expression profiles of both healthy and serous ovarian cancer epithelial samples were considered. We applied a series of bioinformatics methods and tools, including fold-change statistics for differential expression analysis, DisGeNET and NCBI-Gene databases for gene-disease association mapping, DAVID 6.8 for GO enrichment analysis, GeneMANIA for network construction, Cytoscape 3.8 with its plugins for network visualization, analysis, and module detection, the UALCAN for patient survival analysis, and PubChem, DrugBank and DGIdb for gene-drug interaction.ResultsWe identified 8 seed genes that were subjected for drug-gene interaction studies. Because of over-expression in all the four stages of ovarian cancer, we discern that genes HMGA1 and PSAT1 are potential therapeutic biomarkers for its diagnosis at an early stage (stage I). Our analysis suggests that there are 11 drugs common in the seed genes. However, hypermethylated seed genes HMGA1 and PSAT1 showcased a good interaction affinity with drugs cisplatin, cyclosporin, bisphenol A, progesterone, and sunitinib, and are crucial in the proliferation of ovarian cancer.ConclusionOur study reveals that HMGA1 and PSAT1 can be deployed for initial screening of ovarian cancer and drugs cisplatin, bisphenol A, cyclosporin, progesterone, and sunitinib are effective in curbing the epigenetic alteration.

Project description:We are entering the era of personalized medicine in which an individual's genetic makeup will eventually determine how a doctor can tailor his or her therapy. Therefore, it is becoming critical to understand the genetic basis of common diseases, for example, which genes predispose and rare genetic variants contribute to diseases, and so on. Our study focuses on helping researchers, medical practitioners, and pharmacists in having a broad view of genetic variants that may be implicated in the likelihood of developing certain diseases. Our focus here is to create a comprehensive database with mobile access to all available, authentic and actionable genes, SNPs, and classified diseases and drugs collected from different clinical and genomics databases worldwide, including Ensembl, GenCode, ClinVar, GeneCards, DISEASES, HGMD, OMIM, GTR, CNVD, Novoseek, Swiss-Prot, LncRNADisease, Orphanet, GWAS Catalog, SwissVar, COSMIC, WHO, and FDA. We present a new cutting-edge gene-SNP-disease-drug mobile database with a smart phone application, integrating information about classified diseases and related genes, germline and somatic mutations, and drugs. Its database includes over 59 000 protein-coding and noncoding genes; over 67 000 germline SNPs and over a million somatic mutations reported for over 19 000 protein-coding genes located in over 1000 regions, published with over 3000 articles in over 415 journals available at the PUBMED; over 80 000 ICDs; over 123 000 NDCs; and over 100 000 classified gene-SNP-disease associations. We present an application that can provide new insights into the information about genetic basis of human complex diseases and contribute to assimilating genomic with phenotypic data for the availability of gene-based designer drugs, precise targeting of molecular fingerprints for tumor, appropriate drug therapy, predicting individual susceptibility to disease, diagnosis, and treatment of rare illnesses are all a few of the many transformations expected in the decade to come.

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Expression genomics in breast cancer research: microarrays at the crossroads of biology and medicine.

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