Dataset Information

Modelling of hypoxia gene expression for three different cancer cell lines.

ABSTRACT: Gene dynamic analysis is essential in identifying target genes involved pathogenesis of various diseases, including cancer. Cancer prognosis is often influenced by hypoxia. We apply a multi-step pipeline to study dynamic gene expressions in response to hypoxia in three cancer cell lines: prostate (DU145), colon (HT29), and breast (MCF7) cancers. We identified 26 distinct temporal expression patterns for prostate cell line, and 29 patterns for colon and breast cell lines. The module-based dynamic networks have been developed for all three cell lines. Our analyses improve the existing results in multiple ways. It exploits the time-dependence nature of gene expression values in identifying the dynamically significant genes; hence, more key significant genes and transcription factors have been identified. Our gene network returns significant information regarding biologically important modules of genes. Furthermore, the network has potential in learning the regulatory path between transcription factors and the downstream genes. In addition, our findings suggest that changes in genes BMP6 and ARSJ expression might have a key role in the time-dependent response to hypoxia in breast cancer.

SUBMITTER: Soltanalizadeh B

PROVIDER: S-EPMC7061283 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Modelling of hypoxia gene expression for three different cancer cell lines.

Soltanalizadeh Babak B Gonzalez Rodriguez Erika E Maroufy Vahed V Zheng W Jim WJ Wu Hulin H

International journal of computational biology and drug design 20200207 1

Gene dynamic analysis is essential in identifying target genes involved pathogenesis of various diseases, including cancer. Cancer prognosis is often influenced by hypoxia. We apply a multi-step pipeline to study dynamic gene expressions in response to hypoxia in three cancer cell lines: prostate (DU145), colon (HT29), and breast (MCF7) cancers. We identified 26 distinct temporal expression patterns for prostate cell line, and 29 patterns for colon and breast cell lines. The module-based dynamic ...[more]

PMID: 32153660

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Project description:Ovarian cancer has the highest mortality of all of the gynecological malignancies. There are several distinct histotypes of this malignancy characterized by specific molecular events and clinical behavior. These histotypes have differing responses to platinum-based drugs that have been the mainstay of therapy for ovarian cancer for decades. For histotypes that initially respond to a chemotherapeutic regime of carboplatin and paclitaxel such as high-grade serous ovarian cancer, the development of chemoresistance is common and underpins incurable disease. Recent discoveries have led to the clinical use of PARP (poly ADP ribose polymerase) inhibitors for ovarian cancers defective in homologous recombination repair, as well as the anti-angiogenic bevacizumab. While predictive molecular testing involving identification of a genomic scar and/or the presence of germline or somatic BRCA1 or BRCA2 mutation are in clinical use to inform the likely success of a PARP inhibitor, no similar tests are available to identify women likely to respond to bevacizumab. Functional tests to predict patient response to any drug are, in fact, essentially absent from clinical care. New drugs are needed to treat ovarian cancer. In this review, we discuss applications to address the currently unmet need of developing physiologically relevant in vitro and ex vivo models of ovarian cancer for fundamental discovery science, and personalized medicine approaches. Traditional two-dimensional (2D) in vitro cell culture of ovarian cancer lacks critical cell-to-cell interactions afforded by culture in three-dimensions. Additionally, modelling interactions with the tumor microenvironment, including the surface of organs in the peritoneal cavity that support metastatic growth of ovarian cancer, will improve the power of these models. Being able to reliably grow primary tumoroid cultures of ovarian cancer will improve the ability to recapitulate tumor heterogeneity. Three-dimensional (3D) modelling systems, from cell lines to organoid or tumoroid cultures, represent enhanced starting points from which improved translational outcomes for women with ovarian cancer will emerge.

Dataset Information

Modelling of hypoxia gene expression for three different cancer cell lines.

Publications

Modelling of hypoxia gene expression for three different cancer cell lines.

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