Project description:This study set out to establish whether sub-populations of chronic lymphocytic leukaemia (CLL) cells, with different expression of cell surface TLR9 expression, have altered gene transcription signatiures.
Project description:We collected three timepoint blood samples from a CLL patient underwent BTK inhibitor treatment. We performed single cell RNA sequencing on these samples to track expression heterogeneity of malignant B-cell populations over time.
Project description:Evaluation of differential expression between CLL patients in a chemoimmunotherapy trial with age-matched controls 41 CLL tumor samples and 11 age matched controls run on both Affy U133A and U133B chips
Project description:Worldwide, breast cancer is the main cause of cancer mortality in women. Most cases originate in mammary ductal cells that secrete the nipple aspirate fluid (NAF). In cancer patients, this breast secretome contains proteins associated with the tumor microenvironment. NAF studies are challenging because inter-individual variability is substantial. To better address this limitation, we introduced a paired-proteomic strategy that relies on NAF sample analysis from both breasts of patients with unilateral breast cancer. We developed a software extension to the PatternLab for Proteomics software to take advantage of this setup. Briefly, the software relies on a peptide-centric approach and uses the binomial distribution to attribute a probability for each peptide as being linked to the disease or not; these probabilities are then propagated to a final protein p-value according to the Stouffer’s Z-score method. Our approach was applied to both a discovery-driven (shotgun) analysis of NAF samples and a hypothesis-driven (targeted) assessment of 19 cancer-related proteins described in the literature. Shotgun results culminated in the reliable quantitative proteomic profiling of NAF samples from healthy and cancer cohorts. A total of 1,083 proteins were identified, of which 77 were differentially abundant, being mainly involved in glycolysis (Warburg effect) and immune system activation (activated stroma). Additionally, in the estrogen receptor-positive subgroup, proteins related to the lipid metabolism and the complement cascade displayed higher abundance, as expected for this well-differentiated subtype of cancer. The targeted analysis of NAF samples from triple negative patients revealed three differentially abundant proteins related to cell migration/attraction and tumor cell differentiation. In summary, we debuted a paired differential bioinformatics workflow, performing a proof-of-principal differential proteomic analysis of NAF samples in unilateral breast cancers patients. The results revealed a promising statistical paired analysis workflow, thus validating NAF as a treasure-trove for studying this paired-organ cancer type.
Project description:Many functional consequences of mutations on tumor phenotypes in chronic lymphocytic leukemia (CLL) are only partially known. This is in part due to a scarcity of information on the proteome of CLL. We profiled the proteome of 117 CLL samples with data-independent acquisition mass spectrometry (DIA-MS) and integrated the results with genomic, transcriptomic, functional data and clinical outcome. We found trisomy 12 and IGHV to be major determinants of proteome variation in CLL (1055 and 542 differential proteins FDR of 5%). Trisomy 12 was associated with limited protein abundance buffering. Protein complex analyses detected functional units involved in BCR/PI3K/AKT signaling in CLL with trisomy 12. We associated protein expression with response to anticancer drugs, and STAT2 protein expression emerged as a biomarker for the prediction of response to kinase inhibitors including BTK and MEK inhibitors. STAT2 protein levels were determined by gene dosage (trisomy 12), stabilization in a protein complex and linked to interferon signaling in CLL. This study highlights the emerging importance of protein abundance profiling in CLL biology.
Project description:Genome wide DNA methylation profiling of paired adjacent and hepatocellular samples and 8 non-diseased liver samples. The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs. Samples included 12 paired adjacent and 12 hepatocellular samples.
Project description:The aim is to identify the differential miRNA expression profile of B-CLL stimulated with different type of stimulation CPG One color design, 36 samples, Two-condition experiment, CPG-stimulated B-CLL unmutated and mutated vs. Unstimulated B-CLL unmutated and mutated. Biological replicates: 18 unstimulated replicates, 18 CPG-stimulated replicates.