Project description:Cervical cancer is the one of the most common cancer type among women worldwide, with Human Papillomavirus (HPV) playing a causal role in this disease. We applied a novel integrative approach to understand the disease process and find its major drivers. We performed a meta-analysis of gene expression and chromosomal aberration studies comprising data on over 500 patients for the reconstruction of a regulatory meta-network. We found that two sub-networks representing cell cycle and antiviral response (largely involving interferon pathways) were driven by chromosomal amplifications of key regulator genes. In the majority of patients, the two types of drivers were located in the same regions of chromosomal aberrations on 3q, 1q and 1p suggesting that a synergistic effect of both processes is necessary for cervical oncogenesis. In addition, our results revealed a cause of antiviral response in the tumor supporting a model of cervical carcinogenesis in which the loss of episomal HPV mediated by immune response promotes the expression of integrated viral oncogenes and tumor progression. This series is a part of meta-analysis on gene expression in cervical cancer Forty cervical cancer biopsies and twenty normal adjacent tissue samples were obtained from patients with cervical squamous cell carcinomas. Twelve tumor samples were hybridized as pools of two samples, due to RNA quantity limitations. So, in total, there are 34 cervical cancer and 20 normal sample arrays. We used an internal reference design, where the reference RNA sample consisted of a pool of amplified RNAs from cervical cancer biopsies.
Project description:Cervical cancer is the one of the most common cancer type among women worldwide, with Human Papillomavirus (HPV) playing a causal role in this disease. We applied a novel integrative approach to understand the disease process and find its major drivers. We performed a meta-analysis of gene expression and chromosomal aberration studies comprising data on over 500 patients for the reconstruction of a regulatory meta-network. We found that two sub-networks representing cell cycle and antiviral response (largely involving interferon pathways) were driven by chromosomal amplifications of key regulator genes. In the majority of patients, the two types of drivers were located in the same regions of chromosomal aberrations on 3q, 1q and 1p suggesting that a synergistic effect of both processes is necessary for cervical oncogenesis. In addition, our results revealed a cause of antiviral response in the tumor supporting a model of cervical carcinogenesis in which the loss of episomal HPV mediated by immune response promotes the expression of integrated viral oncogenes and tumor progression. This series is a part of meta-analysis on gene expression in cervical cancer
Project description:A growing number of studies on gynecological cancers (GCs) have revealed potential gene markers associated either with the pathogenesis and progression of the disease on representing putative targets for therapy and treatment of cervical (CC), endometrial (EC) and vulvar cancer (VC). However, quite a little overlap is found between these data. In this study we combined data from the three GCs integrating gene expression profile analysis. The meta-analysis including our results and data emerge from other available studies on gynecological malignancies and other cancer types, revealed common properties among them including deregulation of cell cycle, immune response, antiviral response and apoptosis.
Project description:A growing number of studies on gynecological cancers (GCs) have revealed potential gene markers associated either with the pathogenesis and progression of the disease on representing putative targets for therapy and treatment of cervical (CC), endometrial (EC) and vulvar cancer (VC). However, quite a little overlap is found between these data. In this study we combined data from the three GCs integrating gene expression profile analysis. The meta-analysis including our results and data emerge from other available studies on gynecological malignancies and other cancer types, revealed common properties among them including deregulation of cell cycle, immune response, antiviral response and apoptosis. Total RNA was extracted from physiological and cancer patients from cervix, endometrium and vulvar tissue and was hybridized on Affymetrix HG133_A_2.0 microarray chips corresponding to more than 12.000 uniquely represented genes. A total of 35 samples were used to identify potential biomarkers and signatures in each type of cancer.
Project description:In this study, depending on quantitative liposome and transcriptomic analyses, we unveiled safflower seed lipidic landscapes at 5 different developmental stages of seeds and revealed a parallel classification of 417 lipid compounds and their co-expressed genes into 7 distinct lipidic metabolites vs gene modules (MM vs GM). An essential transcriptional regulatory network for major lipid compounds changes that occurred throughout the seed growth cycle was constructed via integrative bioinformatics coupled with functional genomic assays. Sixteen transcription factors were identified that regulate the accumulation of triacylglycerols (TAGs) and fatty acids (FAs). Our findings thus shed light on the seeds of safflower metabolic regulatory network involved in the biosynthesis of major lipid compounds and provide a prospective resource for the designed improvement of oilseed quality.
Project description:Time course gene-expression profiling was conducted in human lymphoblastoid cell lines (LUCY) after exposure with 1Gy and 10Gy gamma irradiation. Differentially expressed genes were identified using natural cubic spline regression modeling (NCSRM) and subsequently subjected to gene regulatory network reconstruction using a partial correlation approach (GeneNet) followed by analysis of the network. Senescence-associated signalling was identified as the chief regulatory network of radiation sensitivity of normal cells.
Project description:We performed integrative gene dosage and expression profiling to identify candidate target genes of the prognostic 3p loss in cervical cancer. Candidate target genes were proposed from the correlation between gene dosage and gene expression. Combined network, gene set, and gene ontology analysis of the gene expression profiles depicted interaction partners of the candidate targets and proposed biological processes that were affected by the 3p loss. Gene dosages from array CGH data (previously submiited to ArrayExpress) were correlated with Illumina gene expression data in the integrative patient cohort. The prognostic significance of the candidate target genes was validated based on the Illumina gene expression data of the validation cohort. Changes in gene expressions after knockdown of three candidate targets, RYBP, TMF1 and PSMD6, were studied by Illumina beadarrays in the cervical cancer cell lines HeLa, SiHa and CaSki.
Project description:Colorectal carcinoma is a major health problem. As a malignant tumor, the malignant potential of colorectal carcinoma is based mainly on its ability to metastasis to different sites. Fascin-1 is an actin binding protein which is involved in reconstruction of intracellular actin network, the latter enforces the neoplastic cell to invade surrounding structures.