Project description:Chronic inflammatory bowel disease (IBD) is associated with an increased risk of colorectal cancer (CRC) in historical cohorts. The pathways of oncogenesis of these CRCs, which are very different clinically from de novo CRCs, are currently unknown. The aim of our work is to identify specific molecular signatures of CRC occurring in the setting of IBD.
Project description:Transcriptomic analysis of fresh breast cancer tissue versus normal tissues. The Study comprising 45 Saudi-Arabian subjects was designed to take advantage of transcriptomics to prospectively explore the roles of lifestyle and genetic susceptibility in the occurrence of breast cancer. Total RNA isolated from 45 surgically resected breast cancer tissues and 8 healthy breast tissues (3 from Affymetrix) and purified, labeled, and hybridized to Affymetrix Human Gene 1.0 ST Array.
Project description:The purpose of this study was to map the landscape of metabolic-transcriptional alterations in glioblastoma multiforme. Omic-datasets were acquired by metabolic profiling (1D-NMR spectroscopy n=33 Patient) and transcriptomic profiling (n=48 Patients). Both datasets were analyzed by integrative network modeling. The computed model concluded in four different metabolic-transcriptomic signatures containing: oligodendrocytic differentiation, cell-cycle functions, immune response and hypoxia. These clusters were found being distinguished by individual metabolism and distinct transcriptional programs. The study highlighted the association between metabolism and hallmarks of oncogenic signaling such as cell-cycle alterations, immune escape mechanism and other cancer pathway alterations. In conclusion, this study showed the strong influence of metabolic alterations in the wide scope of oncogenic transcriptional alterations.
Project description:Ageing is a complex process with common and distinct features across tissues. Unveiling the underlying processes driving ageing in individual tissues is indispensable to decipher the mechanisms of organismal longevity. C. elegans is a well-established model organism that has spearheaded ageing research with the discovery of numerous genetic pathways controlling its lifespan. However, it remains challenging to dissect the ageing of worm tissues due to the limited description of tissue pathology and access to tissue-specific molecular changes during ageing. In this study, we isolated cells from five major tissues in young and old worms and profiled the age-induced transcriptomic changes within these tissues. We observed a striking diversity of ageing across tissues and identified different sets of longevity regulators therein. In addition, we found novel tissue-specific factors, including irx-1 and myrf-2, which control the integrity of the intestinal barrier and sarcomere structure during ageing, respectively. This study demonstrates the complexity of ageing across worm tissues and highlights the power of tissue-specific transcriptomic profiling during ageing, which can serve as a resource to the field.
Project description:A sensitive assay to identify biomarkers that can accurately diagnose the onset of breast cancer using non-invasively collected clinical specimens is ideal for early detection. In this study, we have conducted a prospective sample collection and retrospective blinded validation (PRoBE design) to evaluate the performance and translational utilities of salivary transcriptomic and proteomic biomarkers for the non-invasive detection of breast cancer. The Affymetrix HG U133 Plus 2.0 Array and 2D-DIGE were used to profile transcriptomes and proteomes in saliva supernatants respectively. Significant variations of salivary transcriptomic and proteomic profiles were observed between breast cancer patients and healthy controls. Eleven transcriptomic biomarker candidates and two proteomic biomarker candidates were selected for a preclinical validation using an independent sample set. Transcriptomic biomarkers were validated by RT-qPCR and proteomic biomarkers were validated by quantitative protein immunoblot. Eight mRNA biomarkers and one protein biomarker have been validated for breast cancer detection, yielding ROC-plot AUC values between 0.665 and 0.959. This report provides proof of concept of salivary biomarkers for the non-invasive detection of breast cancer. The salivary biomarkers’ discriminatory power paves the way for a PRoBE-design definitive validation study. Keywords: Salivary biomarker, Breast cancer, Early detection, Salivary transcriptome, Salivary proteome This study, which was approved by the UCLA and Cedars-Sinai Medical Center Institutional Review Boards (#06-07-043 and #3870, respectively), started sample collection in February 2007. The sample collection followed the PRoBE principle (prospective specimen collection). The saliva bank for breast cancer project at the UCLA Dental Research Institute in collaboration with Cedars Sinai Medical Center has collected 200 saliva samples since 2007 with all subjects recruited from the Saul and Joyce Brandman Breast Cancer Center. Of these, 113 samples, including 41 breast cancer patients and 72 healthy control individuals, were selected for the discovery and validation phase of this study. Inclusion criteria of cancer patients consisted of a confirmed diagnosis of breast cancer. Exclusion criteria of cancer patients included therapy/surgery and/or a diagnosis of other malignancies within 5 years prior to saliva collection. Exclusion criteria of control patients included a diagnosis of any malignancies within 5 years prior to saliva collection. Written informed consents and questionnaire data sheets were obtained from all patients who agreed to serve as saliva donors. Unstimulated saliva samples were consistently collected, stabilized, and preserved as previously described. The sample supernatants were reserved at -80 C prior to assay. This study consisted of a discovery phase, followed by an independent preclinical validation phase. Of the 113 samples, 10 breast cancer samples and 10 healthy control samples were chosen for the discovery phase. All breast cancer cases are invasive ductal carcinoma (IDC), the most common type of breast cancer. Biomarkers identified from the discovery studies were first verified using the discovery sample set. An independent sample set, including 31 breast cancer patients and 62 healthy control subjects, was used for the biomarker validation phase.
Project description:Atherosclerosis is the main cause of many cardiovascular and cerebrovascular diseases (CVDs), and gaining a deeper understanding of the intercellular connections and key central genes which mediate formation of atherosclerotic plaques is required. We performed a comprehensive bioinformatics analysis of differential genetic screening, Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway annotation, protein-protein interactions (PPIs), pseudo-timing, intercellular communication, transcription factors on carotid single-cell sequencing data, and aortic bulk transcriptome and metabolomic data. Ten cell types were identified in the data: T cells, monocytes, smooth muscle cells, endothelial cells, B cells, fibroblasts, plasma cells, mast cells, dendritic cells, and natural killer cells. Endothelial, fibroblast, macrophage, and smooth muscle cell subtype differentiation trajectories, interaction networks, and important transcription factors were characterized in detail. Finally, using this information combined with transcriptome and metabolome analyses, we found the key genes and signaling pathways of atherosclerosis, especially the advanced glycation end products and receptor for advanced glycation end products signaling pathway (AGE-RAGE signaling pathway) in diabetic complications, linked the differential metabolites with fibroblasts and atherosclerosis and contributed to it in patients with diabetes. Collectively, this study provides key genes, signaling pathways, cellular communication, and transcription factors among endothelial cells, fibroblasts, macrophages, and smooth muscle cells for the study of atherosclerotic plaques, and provides a basis for the diagnosis and treatment of atherosclerosis-like sclerosis.