Dataset Information

Tissue Proteome Profiling of Ovarian cancer in Pakistani Population.

ABSTRACT: Ovarian cancer is the 5th main cause of death from cancer in females, worldwide. An early and accurate diagnosis of ovarian carcinoma is likely to improve clinical outcome of patients in terms of reduced morbidity and mortality. The objective of our project is the proteome profiling of ovarian malignant and non-malignant tissue samples to find potential biomarkers of disease diagnosis and prognosis. In this project, we have used a systematic protein profiling approach involving 2-dimensional gel electrophoresis coupled with MALDI-TOF MS analysis for identification of biomarkers of ovarian cancer. The associated research paper is in preparation.

INSTRUMENT(S): ultraflex

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Ovary, Left Ovary, Right Ovary

DISEASE(S): Malignant Neoplasm Of Ovary

SUBMITTER: Muhammad Akhtar

LAB HEAD: Muhammad Akhtar, School of Biological Sciences, University of the Punjab, Lahore, Pakistan

PROVIDER: PXD013827 | Pride | 2019-11-27

REPOSITORIES: Pride

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Publications

Upregulated Expression of Calcium-Dependent Annexin A6: A Potential Biomarker of Ovarian Carcinoma.

Noreen Shahzadi S Gardner Qurratulann Afza QA Fatima Iram I Sadaf Saima S Akhtar Muhammad Waheed MW

Proteomics. Clinical applications 20200109 2

<h4>Purpose</h4>An early and accurate diagnosis of ovarian carcinoma (OC) may reduce morbidity and mortality of the patients. To improve the clinical outcome in OC patients, the present study is aimed at identifying robust biomarkers for early OC diagnosis. EXPERIMENTAL DESIGN: In order to look for early-stage protein markers, a systematic protein profiling approach involving 2-dimensional electrophoresis coupled with mass spectrometric analyses of human malignant and non-malignant ovarian biops ...[more]

PMID: 31747122

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Project description:The side population (SP), recently identified in several normal tissues and in a variety of tumors, may comprise cells endowed with stem cell features. In this study, we investigated the presence of SP in epithelial ovarian cancer (EOC) and found it in 4 out of 6 primary cultures from xenotransplants, as well as in 9 out of 25 clinical samples analyzed. SP cells from one xenograft bearing a large SP fraction were characterized in detail and they were capable of recreate the full repertoire of cancer cell populations observed in the parent tumor. Moreover, SP cells had higher proliferation rates, were much less apoptotic compared to non-SP cells, and generated tumors more rapidly than non-SP cells. We also investigated the effects of interferon-alfa (IFN-alpha), a cytokine which has been widely used to treat solid tumors, on EOC cells and observed that IFN-alpha exerts marked anti-proliferative and pro-apoptotic effects on primary cultures containing SP cells. IFN-alfa-treatment invariably caused a dramatic reduction in SP size in tumor cell lines of different origin and in normal bone-marrow SP cells, associated with a distinctive transcriptional profile. Gene therapy with human IFN-alpha resulted in regression of established tumors bearing a large SP fraction, which was not observed when tumors bearing low SP levels were treated. These findings could have relevant clinical implications since they imply that tumors bearing large SP numbers - albeit rare - could be sensitive to IFN-alpha treatment. Experiment Overall Design: 4 Affymetrix microarrays: Experiment Overall Design: 2 technical replicates: Ovarian cancer, untreated Side Population, rep1 Experiment Overall Design: Ovarian cancer, untreated Side Population, rep2 Experiment Overall Design: + Experiment Overall Design: 2 technical replicates: Ovarian cancer, IFN-alpha treated Side Population, rep1 Experiment Overall Design: Ovarian cancer, IFN-alpha treated Side Population, rep2

Project description:Background: Malignant ascites is often present at diagnostic in women with advanced ovarian cancer (OC) and its presence is associated with a worse outcome. Human peritoneal mesothelial cells (HPMCs) are key components of malignant ascites. Although the interplay between HPMCs and OC cells is believed to be critical for tumor progression, it has not been well characterized. The purpose of this study was to assess the effect of ascites on HPMCs and clarify the role of HPMCs in OC progression. Methods: Human OC ascites and benign peritoneal fluids were assessed for their ability to stimulate HPMC proliferation. Conditioned medium from ascites- and benign fluid-stimulated HPMCs were compared for their ability to attenuate apoptosis induced by TNF-related apoptosis-inducing ligand (TRAIL). We conducted a comparative analysis of global expression changes in ascites-stimulated HPMCs using Agilent oligonucleotide microarrays. Results: As compared to benign peritoneal fluids, malignant ascites stimulated the proliferation of HPMCs. TRAIL-induced apoptosis was attenuated in OC cells exposed to conditioned medium from ascites-stimulated HPMCs as compared to OC cells exposed to conditioned medium from benign fluid-stimulated HPMCs. A total of 649 genes were differentially expressed in ascites-stimulated HPMCs. Based on a ratio of more than 1.5-fold and a P < 0.05, 484 genes were up-regulated and 165 genes were down-regulated in ascites-exposed HPMCs. Stimulation of HPMCs with OC ascites resulted in differential expression of genes mainly associated with the regulation of cell growth and proliferation, cell death, cell cycle and cell assembly and organization, compared to benign peritoneal fluids. Top networks up-regulated by OC ascites included Akt and NF-M-NM-:B survival pathways whereas vascular endothelial growth factor (VEGF) pathway was down-regulated. Conclusions: The results of this study not only provide evidence supporting the importance of the interplay between cancer cells and HPMCs but also define the role that the tumor environment plays in these interactions. The expression profiles from human peritoneal mesothelial cells (HPMC) cultures exposed to peritoneal fluids and ovarian cancer ascites were compared using the Agilent Whole Human Genome Oligonucleotide microarrays, containing 44,000 genes. Microarrays were performed on HPMCs exposed to 3 malignant ascites from women with advanced (stage III/IV) serous OC and two benign peritoneal fluids. First, we generated lists of significantly up-regulated and down-regulated genes that were differentially expressed between OC ascites (OVC346, OVC508 and OVC509) and control OV370 peritoneal fluid. Then, the set of genes that were commonly expressed between control peritoneal fluids (OV370 and OV401) were subtracted from the first list of genes to generate a dataset of differentially expressed genes between malignant ascites and benign peritoneal fluids.

Dataset Information

Tissue Proteome Profiling of Ovarian cancer in Pakistani Population.

Publications

Upregulated Expression of Calcium-Dependent Annexin A6: A Potential Biomarker of Ovarian Carcinoma.

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