scholarly journals Identification and Characterization of Metastasis-Associated Individualized Gene Expression Signature in Osteosarcoma

2020 ◽  
Author(s):  
Guofeng Zhang ◽  
Yonglin Zhu ◽  
Chengzhen Jin ◽  
Baisui Zhou ◽  
Shanrun Zhao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cancer Metastasis ◽  
Gene Expression Signature ◽  
Strong Positive Correlation ◽  
Computational Pipeline ◽  
Drug Candidates ◽  
Relative Expression Orderings ◽  
Identification And Characterization ◽  
Metastasis Associated Gene

Abstract Background: Osteosarcoma (OS) patients with surgical resection still relapse with poor prognosis due to the inability to detect distant metastasis. It’s essential to identify metastasis-related biomarkers for OS. Methods: Here, a computational pipeline follow relative expression orderings (REOs) using gene expression was constructed in metastases and non-metastases OS patients. Results: 138 metastasis-associated gene pair signatures (MGPSs) were identified follow two independent datasets. A metastases-specific co-expressed MGPS network was constructed for extracting biomarker for clinical application. MGPS such as MYL5 and RPL27A showed strong positive correlation (Cor =0.75, P <0.001). There were thirteen prognostic MGPSs in above network. These prognostic MGPSs could become as a specific classifier to distinguish metastases and non-metastases OS patients. MGPSs were associated with cancer metastasis-related functions. Drug and MGPS network could provide some drug candidates for treatment of OS. Conclusions: Collectively, the roles of the MGPSs in OS were elucidated, which could be beneficial for understanding OS pathogenesis and treatment.

scholarly journals Identification and characterization of metastasis-associated individualized gene expression signature in osteosarcoma

2020 ◽  
Author(s):  
Guofeng Zhang ◽  
Yonglin Zhu ◽  
Chengzhen Jin ◽  
Baisui Zhou ◽  
Shanrun Zhao ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cancer Metastasis ◽  
Gene Expression Signature ◽  
Strong Positive Correlation ◽  
Drug Candidates ◽  
Complete Surgical Resection ◽  
Relative Expression Orderings ◽  
Identification And Characterization ◽  
Metastasis Associated Gene

Abstract Introduction: Osteosarcoma (OS) patients with complete surgical resection still relapse with poor prognosis. Part of this is due to the inability to accurately detect distant metastasis. Thus it’s enssential to identify metastasis-related biomarkers for OS.Methods: In present study, a computational pipeline based on relative expression orderings (REOs) using gene expression proles was constructed in metastases and non-metastases OS patients. Results: 138 metastasis-associated gene pair signature (MGPS) were identified follow two independent datasets. In order to further extract metastasis-associated biomarker for clinical application, a metastases-specific co-expressed MGPS network was constructed and analyzed. MGPS such as MYL5 and RPL27A showed strong positive correlation (Cor =0.75, P <0.001) in metastatic OS patients. There were thirteen MGPSs in above network were associated with prognosis. These prognostic MGPSs could become as a specific classifier to distinguish metastases and non-metastases OS patients. Functional analysis showed MGPSs were associated with cancer metastasis-related functions. Drug and MGPS network could provide some drug candidates for treatment of OS. Conclusions: Collectively, the roles of the MGPSs in OS were elucidated, which could be beneficial for understanding OS pathogenesis and treatment.

scholarly journals A Novel Triple-Fluorescent HCMV Strain Reveals Gene Expression Dynamics and Anti-Herpesviral Drug Mechanisms

2021 ◽  
Vol 10 ◽  
Author(s):  
Ulfert Rand ◽  
Tobias Kubsch ◽  
Bahram Kasmapour ◽  
Luka Cicin-Sain
Keyword(s):  
Gene Expression ◽  
Hcmv Infection ◽  
Viral Fitness ◽  
High Temporal Resolution ◽  
Detection Techniques ◽  
Drug Candidates ◽  
New Drug ◽  
Gene Expression Dynamics ◽  
Identification And Characterization

Human Cytomegalovirus (HCMV) infection may result in severe outcomes in immunocompromised individuals such as AIDS patients, transplant recipients, and neonates. To date, no vaccines are available and there are only few drugs for anti-HCMV therapy. Adverse effects and the continuous emergence of drug-resistance strains require the identification of new drug candidates in the near future. Identification and characterization of such compounds and biological factors requires sensitive and reliable detection techniques of HCMV infection, gene expression and spread. In this work, we present and validate a novel concept for multi-reporter herpesviruses, identified through iterative testing of minimally invasive mutations. We integrated up to three fluorescence reporter genes into replication-competent HCMV strains, generating reporter HCMVs that allow the visualization of replication cycle stages of HCMV, namely the immediate early (IE), early (E), and late (L) phase. Fluorescent proteins with clearly distinguishable emission spectra were linked by 2A peptides to essential viral genes, allowing bicistronic expression of the viral and the fluorescent protein without major effects on viral fitness. By using this triple color reporter HCMV, we monitored gene expression dynamics of the IE, E, and L genes by measuring the fluorescent signal of the viral gene-associated fluorophores within infected cell populations and at high temporal resolution. We demonstrate distinct inhibitory profiles of foscarnet, fomivirsen, phosphonoacetic acid, ganciclovir, and letermovir reflecting their mode-of-action. In conclusion, our data argues that this experimental approach allows the identification and characterization of new drug candidates in a single step.

scholarly journals Identification and Characterization of Optimal Gene Expression Markers for Detection of Breast Cancer Metastasis

2005 ◽  
Vol 7 (3) ◽  
pp. 327-336 ◽  
Author(s):  
John Backus ◽  
Todd Laughlin ◽  
Yixin Wang ◽  
Robert Belly ◽  
Robert White ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Identification And Characterization

Association of hypoxia-induced centrosome amplification with clinical outcomes in triple-negative breast cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e23170-e23170
Author(s):  
Karuna Mittal ◽  
Da Hoon Choi ◽  
Angela Ogden ◽  
Brian D Melton ◽  
Meenakshi Vij Gupta ◽  
...  
Keyword(s):  
Gene Expression ◽  
Triple Negative ◽  
Gene Expression Signature ◽  
Breast Tumors ◽  
Centrosome Amplification ◽  
Strong Positive Correlation ◽  
Breast Cancers ◽  
Tissue Samples ◽  
Hypoxic Conditions ◽  
Cells Cultured

e23170 Background: Centrosome amplification (CA) which refers to presence of supernumerary or abnormally large centrosomes is believed to drive tumor progression by promoting chromosomal instability and the generation of aggressive tumor clones that are more capable of rapid metastasis. Not much is known about factors that drive CA within solid tumors. We have previously shown the existence of rampant CA in triple-negative breast cancers (TNBCs).We report here thatintratumoral hypoxia, which is one of the major contributors to tumor heterogeneity, induces CA in TNBCs via HIF-1α. Methods: We immunohistochemically labeled 24 TNBC and adjacent normal tissue samples for HIF-1α and derived weighted indices (WIs) for nuclear HIF-1α. Adjacent serial sections from the same tumors were immunofluorescently labeled for the centrosomal marker γ-tubulin and CA was determined. Using public microarray datasets (Kao dataset, n = 327), we investigated whether centrosomal gene expression is enriched in breast tumors characterized by a hypoxia gene expression signature. Finally, to test the role of hypoxia in CA induction we exposed cultured TNBC cells (MDA-MB-231 and MDA-MB-468) to hypoxia and overexpressed (OE) or knocked out (KO) HIF-1α and quantitated CA. Results: A strong positive correlation was found between nuclear HIF-1α WI and CA in TNBC samples (Spearman’s rho p = 0.722, p < 0.001), and higher nuclear HIF-1α was associated with worse overall survival (p = 0.041; HR = 1.03). Furthermore, breast tumors with high expression of hypoxia-associated genes exhibited higher expression of centrosomal genes than breast tumors with low expression of hypoxia-associated genes. TNBC cells cultured in hypoxic conditions exhibited ~1.5 fold higher (p < 0.05) CA compared to cells cultured in normoxic conditions. Interestingly, level of CA decreased when HIF-1α KO TNBC cells were exposed to hypoxia; conversely, CA increased when HIF-1α OE TNBC cells were cultured in normoxic conditions. Conclusions: Thus,intratumoral hypoxia drives CA in TNBC via HIF-1α and contributes to poor outcomes. Determination of CA may help identify TNBC patients who could benefit from centrosome declustering drugs and HIF-1α inhibitors.

scholarly journals Identification and characterization of an injury-induced skeletal progenitor

2015 ◽  
Vol 112 (32) ◽  
pp. 9920-9925 ◽  
Author(s):  
Owen Marecic ◽  
Ruth Tevlin ◽  
Adrian McArdle ◽  
Eun Young Seo ◽  
Taylor Wearda ◽  
...  
Keyword(s):  
Gene Expression ◽  
Progenitor Cells ◽  
Expression Patterns ◽  
Gene Expression Patterns ◽  
Cell Type ◽  
Fracture Callus ◽  
Adult Mice ◽  
Induced Changes ◽  
Identification And Characterization

The postnatal skeleton undergoes growth, remodeling, and repair. We hypothesized that skeletal progenitor cells active during these disparate phases are genetically and phenotypically distinct. We identified a highly potent regenerative cell type that we term the fracture-induced bone, cartilage, stromal progenitor (f-BCSP) in the fracture callus of adult mice. The f-BCSP possesses significantly enhanced skeletogenic potential compared with BCSPs harvested from uninjured bone. It also recapitulates many gene expression patterns involved in perinatal skeletogenesis. Our results indicate that the skeletal progenitor population is functionally stratified, containing distinct subsets responsible for growth, regeneration, and repair. Furthermore, our findings suggest that injury-induced changes to the skeletal stem and progenitor microenvironments could activate these cells and enhance their regenerative potential.

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