scholarly journals Genomic Expression Profiles: From Molecular Signatures to Clinical Oncology Translation

Author(s):  
Norfilza M. ◽  
Nor Azian ◽  
Then Sue ◽  
Rahman Jamal
PLoS ONE ◽  
2009 ◽  
Vol 4 (8) ◽  
pp. e6536 ◽  
Author(s):  
Guanghui Hu ◽  
Pankaj Agarwal

Author(s):  
Choong Chin Liew

AbstractTraditional gene expression studies typically focus on one or a few genes of interest. An important limitation of single-gene studies is that they present a portrait of disease that is essentially static. However, disease is a dynamic process, driven by a combination of genetic, epigenetic and environmental factors. Recently, genomic technologies have permitted better characterization of the dynamic aspect of disease progression. Genome-wide expression profiles of cardiovascular diseases, heart failure in particular, using microarrays have been published and are providing new insights into this complex disease. Tissue biopsies required for traditional microarray studies, however, are often invasive and not readily available. By contrast, blood samples are relatively non-invasive and are readily available. In a number of recent studies, blood cells appear to be a viable substitute for tissue biopsy. Blood cells have the ability to mirror the body's tissues and organs in health and disease; thus, we hypothesize that blood cells can indicate at the molecular level the presence of disease. Here we review microarray gene expression profiling of blood RNA for a number of different diseases. Sieving through gene expression molecular signatures has identified groups of genes characteristic of each and has identified biomarkers associated with specific diseases.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9047-9047
Author(s):  
A. E. Rose ◽  
J. Wang ◽  
A. Pearlman ◽  
N. Doudican ◽  
E. Hernando ◽  
...  

9047 Background: Primary nodular melanoma (NM) patients have a relatively poor prognosis compared to superficial spreading melanoma (SSM) patients. The disparity is generally attributed solely to NM's advanced thickness at presentation. In this study we attempted to define molecular signatures of NM and SSM that may explain their clinical differences. Methods: We performed an in silico gene expression analysis of 2 public data sets consisting of 36NM and 54 SSM primary melanoma tissues (CCR 2007;13 and JNCI 2006;98). We then utilized DNA microarray to generate gene expression profiles of a panel of 22 melanoma cell lines (2SSM, 4 NM, 12 met, 4 melanocytes). Differentially expressed genes and over-represented pathways in NM and SSM were identified based on a pooled analysis of the 3 data sets. We then used SNP array to define genomic alterations unique to NM and SSM but not altered in normal melanocytes. Finally, we correlated SNP array with gene expression. Results: Genes significantly overexpressed (p<0.05) in NM showed over-representation of pathways related to MAPK signaling (p=0.05) and cytoskeleton organization (p=0.02), while SSM showed over-representation of cell communication (p=0.05) and primary metabolic processes (p=0.002). Notable correlations between gene expression and copy number alteration in NM include increased copy number/overexpression of SOX5 (transcription factor related to embryonic development and cell fate) and the downregulation/deletion of ST14 (suppression of tumorigenicity 14). SSM demonstrated concordance of increased copy number/overexpression of EZR (cell adhesion protein implicated in human cancer) as well as PALLD (a protein related to motility, adhesion, and extracellular matrix interactions). Notable SSM genes showing correlation between downregulation/deletion include BNIP3 (a pro-apoptotic protein) and MTAP (often co- deleted with tumor suppressor p16). Conclusions: Simultaneous integration of gene expression with SNP array revealed molecular signatures characteristic of NM and SSM. These results suggest that NM and SSM are distinct biologic entities and that molecularly targeted adjuvant therapy may be more effective if tailored to the molecular signatures of melanoma subtypes. Validation is necessary to draw further conclusions. No significant financial relationships to disclose.


2016 ◽  
Vol 28 (11) ◽  
pp. 1798 ◽  
Author(s):  
Li Shao ◽  
Ri-Cheng Chian ◽  
Yixin Xu ◽  
Zhengjie Yan ◽  
Yihui Zhang ◽  
...  

Cumulus cells (CCs) are distinct from other granulosa cells and the mutual communication between CCs and oocytes is essential for the establishment of oocyte competence. In the present study we assessed genomic expression profiles in mouse CCs before and after oocyte maturation in vitro. Microarray analysis revealed significant changes in gene expression in CCs between the germinal vesicle (GV) and metaphase II (MII) stages, with 2615 upregulated and 2808 downregulated genes. Genes related to epidermal growth factor, extracellular matrix (Ptgs2, Ereg, Tnfaip6 and Efemp1), mitochondrial metabolism (Fdx1 and Aifm2), gap junctions and the cell cycle (Gja1, Gja4, Ccnd2, Ccna2 and Ccnb2) were highlighted as being differentially expressed between the two development stages. Real-time polymerase chain reaction confirmed the validity and reproducibility of the results for the selected differentially expressed genes. Similar expression patterns were identified by western blot analysis for some functional proteins, including EFEMP1, FDX1, GJA1 and CCND2, followed by immunofluorescence localisation. These genes may be potential biomarkers for oocyte developmental competence following fertilisation and will be investigated further in future studies.


2016 ◽  
Author(s):  
Feiran Zhang ◽  
Christy Hammack ◽  
Sarah C. Ogden ◽  
Yichen Cheng ◽  
Emily M. Lee ◽  
...  

AbstractZika virus (ZIKV) infection causes microcephaly and has been linked to other brain abnormalities. How ZIKV impairs brain development and function is unclear. Here we systematically profiled transcriptomes of human neural progenitor cells exposed to Asian ZIKVC, African ZIKVM, and dengue virus (DENV). In contrast to the robust global transcriptome changes induced by DENV, ZIKV has a more selective and larger impact on expression of genes involved in DNA replication and repair. While overall expression profiles are similar, ZIKVC, but not ZIKVM, induces upregulation of viral response genes and TP53. P53 inhibitors can block the apoptosis induced by both ZIKVC and ZIKVM in hNPCs, with higher potency against ZIKVC-induced apoptosis. Our analyses reveal virus- and strain-specific molecular signatures associated with ZIKV infection. These datasets will help to investigate ZIKV-host interactions and identify neurovirulence determinants of ZIKV.


2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaoting Yao ◽  
Tian Jing ◽  
Tianxing Wang ◽  
Chenxin Gu ◽  
Xi Chen ◽  
...  

Background: Pulmonary arterial hypertension (PAH) is a life-threatening chronic cardiopulmonary disease. However, there are limited studies reflecting the available biomarkers from separate gene expression profiles in PAH. This study explored two microarray datasets by an integrative analysis to estimate the molecular signatures in PAH.Methods: Two microarray datasets (GSE53408 and GSE113439) were exploited to compare lung tissue transcriptomes of patients and controls with PAH and to estimate differentially expressed genes (DEGs). According to common DEGs of datasets, gene and protein overrepresentation analyses, protein–protein interactions (PPIs), DEG–transcription factor (TF) interactions, DEG–microRNA (miRNA) interactions, drug–target protein interactions, and protein subcellular localizations were conducted in this study.Results: We obtained 38 common DEGs for these two datasets. Integration of the genome transcriptome datasets with biomolecular interactions revealed hub genes (HSP90AA1, ANGPT2, HSPD1, HSPH1, TTN, SPP1, SMC4, EEA1, and DKC1), TFs (FOXC1, FOXL1, GATA2, YY1, and SRF), and miRNAs (hsa-mir-17-5p, hsa-mir-26b-5p, hsa-mir-122-5p, hsa-mir-20a-5p, and hsa-mir-106b-5p). Protein–drug interactions indicated that two compounds, namely, nedocromil and SNX-5422, affect the identification of PAH candidate biomolecules. Moreover, the molecular signatures were mostly localized in the extracellular and nuclear areas.Conclusions: In conclusion, several lung tissue-derived molecular signatures, highlighted in this study, might serve as novel evidence for elucidating the essential mechanisms of PAH. The potential drugs associated with these molecules could thus contribute to the development of diagnostic and therapeutic strategies to ameliorate PAH.


2003 ◽  
Vol 100 (16) ◽  
pp. 9608-9613 ◽  
Author(s):  
E. C. Gunther ◽  
D. J. Stone ◽  
R. W. Gerwien ◽  
P. Bento ◽  
M. P. Heyes

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