Profiling the cancer proteome

Abstract: Cancer is a complex and heterogeneous disease where cells have started to grow uncontrolled and this disease remains a major health problem. Because of diffuse symptoms it often presents at a late stage. Insufficient understanding of the different phenotypes hinders the development of targeted therapeutics and consequently patients show a diverse range of responses to a given treatment. This thesis is based on four original papers where mass spectrometry based proteomics has been used to study three different cancers; breast, ovarian and prostate cancer. Two-dimensional gel electrophoresis and shotgun proteomics LC-MS/MS based analysis has been applied. Ovarian cancers often have a bad prognosis because of late presentation. Diagnostic markers for early detection are urgently needed. Two studies in this thesis analysed ovarian cancer tumours for this purpose. Protein expression profiles from 2D-DIGE could separate the tumour subgroups and proteins differentially expressed with increased malignancy were identified. A more in-depth characterisation of benign and malignant samples was done using a shotgun proteomics approach and iTRAQ for quantitation. Breast cancer consists of several pathological subtypes with different clinical presentations and outcomes. Using 2D-DIGE protein expression profiles were constructed for tumours previously analysed for gene expression to stratify these tumours. The subgroups found agree very well with groups found on transcriptional level and these correlate well with clinical information. Proteins characterising these subgroups could be useful as prognostic markers in the clinic. Somatostatin can potentially inhibit tumour growth in advance stage hormone refractory prostate cancer. A derivative of somatostatin that increases its half-life is interesting as a potential treatment. The effect of somatostatin and its derivative was studied in a prostate cancer cell line using 2DE. Differentially expressed proteins were identified. Somatostatin and its derivative were shown to exert the same effect on the cell line pointing at the derivate as a potential treatment.