Detection of Colorectal Cancer by Serum and Tissue Protein Profiling: A Prospective Study in a Population at Risk

Colorectal cancer (CRC) is the second most common cause of cancer-related death in Europe and its prognosis is largely dependent on stage at diagnosis. Currently, there are no suitable tumour markers for early detection of CRC. In a retrospective study we previously found discriminative CRC serum protein profiles with surface enhanced laser desorption ionisation—time of flight mass spectrometry (SELDI-TOF MS). We now aimed at prospective validation of these profiles. Additionally, we assessed their applicability for follow-up after surgery and investigated tissue protein profiles of patients with CRC and adenomatous polyps (AP). Serum and tissue samples were collected from patients without known malignancy with an indication for colonoscopy and patients with AP and CRC during colonoscopy. Serum samples of controls (CON; n = 359), patients with AP (n = 177) and CRC (n = 73), as well as tissue samples from AP (n = 52) and CRC (n = 47) were analysed as described previously. Peak intensities were compared by non-parametric testing. Discriminative power of differentially expressed proteins was assessed with support vector machines (SVM). We confirmed the decreased serum levels of apolipoprotein C-1 in CRC in the current population. No differences were observed between CON and AP. Apolipoprotein C-I levels did not change significantly within 1 month post-surgery, although a gradual return to normal levels was observed. Several proteins differed between AP and CRC tissue, among which a peak with similar mass as apolipoprotein C-1. This peak was increased in CRC compared to AP. Although we prospectively validated the serum decrease of apolipoprotein C-1 in CRC, serum protein profiles did not yield SVM classifiers with suitable sensitivity and specificity for classification of our patient groups

Applicability and reproducibility of acute myeloid leukaemia stem cell assessment in a multi-centre setting

Leukaemic stem cells (LSC) have been experimentally defined as the leukaemia-propagating population and are thought to be the cellular reservoir of relapse in acute myeloid leukaemia (AML). Therefore, LSC measurements are warranted to facilitate accurate risk stratification. Previously, we published the composition of a one-tube flow cytometric assay, characterised by the presence of 13 important membrane markers for LSC detection

Mayr Versus Woese : Akaryotes and Eukaryotes

In 1998, on the brink of a great public effort that by now has delivered the sequences of thousands of genomes and has annotated these genomes by translating tens of thousands of 3D protein domain structures from their coding sequences, Ernst Mayr and Carl Woese engaged in a debate. At issue were the virtues of phenotypic contra genotypic approaches to phylogeny and taxonomy. Though not conclusive, this confrontation in retrospect illustrates the defects of both their perspectives and simultaneously illuminates the strengths of the approach to phylogenetic systematics that was favored by Willi Hennig. Hennig’s cladism lends itself well to a rigorous exploitation of genome sequence data in which both the genotypic and phenotypic modes replace the technically questionable gene tree approach to deep phylogeny championed by Woese. Diverse phylogenomic data now suggest that though Mayr’s phenetic arguments were incomplete, his division of organisms into two major taxonomic groups, the akaryotes (formerly the prokaryotes) and eukaryotes, is probably correct. Thus, in a phylogeny based on genome repertoires of protein domains, the universal common ancestor of the three superkingdoms descends in two primary lineages, Akaryote and Eukaryote