Post-operative C-reactive protein as a strong independent predictor of long-term colorectal cancer outcomes: consistent findings from two large patient cohorts.

BACKGROUND: Post-surgery blood-based biomarkers may be useful for guiding treatment and surveillance decisions among colorectal cancer (CRC) patients. However, most candidate biomarkers provide little if any predictive value beyond stage at diagnosis. We aimed to investigate the independent prognostic value of post-operative serum C-reactive protein (CRP), a highly sensitive biomarker of inflammation, for long-term CRC outcomes in two large patient cohorts. MATERIALS AND METHODS: CRP levels were measured from serum samples of CRC patients collected ≥1 month post-surgery in the German DACHS (n = 1416) and the UK Biobank (n = 1149) cohorts. Associations of post-operative CRP with overall survival (OS) and CRC-specific survival (CSS) were assessed using Cox regression and presented as hazard ratios (HRs) with 95% confidence intervals (CIs), adjusted for key sociodemographic and clinical covariates. RESULTS: In both cohorts, consistent strong dose-response relationships between post-operative CRP and both OS and CSS were observed. Adjusted HRs (95% CI) for CRP >10 versus <3 mg/l were 1.93 (1.58-2.35) and 2.70 (2.03-3.59) in the DACHS cohort, and 2.70 (1.96-3.71) and 2.61 (1.83-3.72) in the UK Biobank cohort, respectively. Associations between post-operative CRP and OS were particularly strong among younger patients (<65 years at diagnosis; P value for interaction by age <0.01). CONCLUSIONS: Serum CRP determined a month or more after surgery may be useful as a strong independent prognostic biomarker for guiding therapeutic decisions and for surveillance of the course of disease of CRC patients, particularly those <65 years of age at diagnosis.

Streptococcus pneumoniae: proteomics of surface proteins for vaccine development.

Two formulations of pneumococcal vaccines are currently available to prevent invasive disease in adults and children. However, these vaccines will not protect against the majority of Streptococcus pneumoniae serotypes. The use of highly conserved cell-wall-associated proteins in vaccines may circumvent this problem. A proteomics approach was used to identify 270 S. pneumoniae cell-wall-associated proteins, which were then screened in a process that included in-silico, in-vitro and in-vivo validation criteria. Five potential candidates for inclusion in a vaccine were selected, expressed in Escherichia coli, and purified for use in immunisation experiments. These proteins were detected in at least 40 different serotypes of S. pneumoniae, and were expressed in S. pneumoniae isolates causing infection. Two of the five candidate proteins, the putative lipoate protein ligase (Lpl) and the ClpP protease, resulted in a reduced CFU titre and a trend towards reduced mortality in an animal sepsis model for investigating new S. pneumoniae protein vaccines.

Campylobacter jejuni proteomics for new travellers' diarrhoea vaccines.

Travellers' diarrhoea is defined as diarrhoea that develops while a person is abroad in or shortly after return from a developing country. Different pathogens cause diarrhoea in travellers. Campylobacter jejuni is one of the most prominent agents for this illness. Diarrhoea is defined as an abnormally increased frequency or decreased consistency of stools for less than one week. Antibiotics are effective in preventing travellers' diarrhoea, but routine prophylaxis with antibiotics, should be discouraged. Vaccination is promising but no vaccine against C. jejuni is available at the moment. This article presents the ACE BioSciences strategy for the discovery of protein based vaccine candidates using a cell surface proteomics approach of C. jejuni. New targets for C. jejuni protein vaccines were identified. As proof of concept, we could demonstrate decreased colonization of C. jejuni in mice after vaccination with some of these candidates. It is likely that the proteomics based ACE-Biosciences approach will result in reliable travellers' diarrhoea protein-vaccines in the future.

Novel surface polypeptides of Campylobacter jejuni as traveller's diarrhoea vaccine candidates discovered by proteomics.

Campylobacter jejuni is one of the most common causes of traveller's diarrhoea and food poisoning, therefore development of a vaccine is important. Using biochemical fractionation and mass spectrometry analysis, we identified more than 110 surface polypeptides. Eight C. jejuni identified surface proteins were expressed in Escherichia coli and purified. Mice were immunized with different doses of these purified proteins and challenged orally with C. jejuni strains ML1 and ML53. The degree of protection of mice was tested by intestinal colonization. At least two groups of mice vaccinated with purified proteins clear the infection faster than control mice. Here, we present the use of a proteomics based approach for the identification of novel protein based C. jejuni vaccines for the first time.

Use of mass spectrometric methods for protein identification in receptor research.

In recent years, mass spectrometry has become the method of choice for identifying small amounts of gel separated proteins. Using high mass accuracy peptide mass mapping followed if necessary by nanoelectrospray sequencing, most mammalian proteins can now be identified quickly and sensitively either in amino acid or in EST sequence databases. These methods are illustrated here using an ongoing project in the author's laboratory, a mass spectrometric screen for new mouse brain receptors and their interaction partners.